| Id ↑ | Rare Disease Name ↑ | Prevalance ↑ | Associated Genes↑ | Aliases↑ | Disease Description↑ | Gene Descriptions↑ | Cell Line↑ | |
|---|---|---|---|---|---|---|---|---|
| 1 | 15q13.3 microdeletion syndrome Burnside-Butler syndrome | 1 in 40,000 to 1 in 100,000 individuals in the general population | CHRNA7 | Alpha-7 nicotinic acetylcholine receptor Neuronal acetylcholine receptor subunit alpha-7 Neuronal nicotinic acetylcholine receptor alpha-7 subunit Nicotinic cholinergic receptor alpha-7 subunit Acetylcholine receptor subunit alpha-7 NACHRA7 A7-nAChR nAChR α7 Alpha7 nAChR CHRNA7 protein | 15q13.3 microdeletion syndrome, or Burnside-Butler syndrome, is a genetic disorder due to a deletion on chromosome 15 at region 15q13.3, either de novo or inherited. It leads to developmental delays, intellectual disabilities, autism spectrum disorder, ADHD, anxiety, seizures, and psychiatric disorders like schizophrenia. Physical features may include subtle facial differences, hypotonia, and possible congenital heart defects. Diagnosis involves genetic testing and clinical evaluation. Management includes early intervention, medical treatment, special education, and behavioral therapy. Prognosis varies, and genetic counseling is recommended for affected families | cholinergic receptor nicotinic alpha 7 subunit | SH-SY5Y- Human neuroblastoma cells often used in studies of neurobiology. PC12 - Rat pheochromocytoma cells commonly used in studies of neuronal differentiation. C2C12 - Mouse myoblast cells used in studies of muscle biology. | |
| 2 | 15q24 microdeletion syndrome Chromosome 15q24 deletion syndrome | fewer than 1 in 100,000 individuals | SIN3A | hSIN3A,mSin3A | 15q24 microdeletion syndrome is a rare genetic disorder caused by a deletion in chromosome 15 at the q24 region, leading to developmental delays, intellectual disability, characteristic facial features, congenital malformations, and behavioral issues. Diagnosis is typically through genetic testing, and most cases are de novo. Management involves a multidisciplinary approach with therapies and interventions to address medical and developmental needs. Prognosis varies based on the severity of symptoms, but early and comprehensive care can improve outcomes. | SIN3 transcription regulator family member A | PC12 - Rat pheochromocytoma cells. NIH 3T3 - Mouse fibroblast cells. BJ - Human foreskin fibroblast cells. BJ - Human foreskin fibroblast cells.THP-1 - Human monocytic cells. | |
| 3 | 17p11.2 microduplication syndrome Potocki-Lupski syndrome (PTLS) | fewer than 200 cases reported in the medical literature | SMCR (Smith-Magenis syndrome chromosome region), Retinoic acid-induced 1 Retinoic acid-induced protein 1-like MDS (Mental retardation, autosomal dominant 17) 17p11.2 microdeletion syndrome candidate gene 2 | 17p11.2 microduplication syndrome is a rare genetic disorder caused by a duplication of a segment on chromosome 17 at the p11.2 region. This condition is characterized by developmental delays, intellectual disability, speech and motor skill impairments, behavioral problems, and distinctive facial features. Diagnosis is confirmed through genetic testing, typically chromosomal microarray analysis. Most cases are de novo, though some can be inherited. Management involves a multidisciplinary approach with various therapies to support development and address medical issues. Prognosis varies depending on the duplication's impact, but supportive care can enhance quality of life. | retinoic acid induced 1 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). PC12 (pheochromocytoma cells). C6 (glioma cells). NRK (Normal Rat Kidney cells). | ||
| 4 | 17q11 microdeletion syndrome neurofibromatosis type 1 microdeletion syndrome | 1 in 3,000 to 1 in 4,000 individuals worldwide | NF1 | von Recklinghausen neurofibromatosis gene | 17q11 microdeletion syndrome, also known as NF1 microdeletion syndrome or neurofibromatosis type 1 microdeletion syndrome, is a genetic disorder characterized by the deletion of a segment on chromosome 17 at the q11 region. This condition shares some features with neurofibromatosis type 1 (NF1) but also has distinct characteristics. Common symptoms include developmental delays, intellectual disability, learning difficulties, distinctive facial features, and an increased risk of neurofibromas and other tumors. Diagnosis is typically made through genetic testing, specifically detecting the deletion in the NF1 gene region. Management involves a multidisciplinary approach to address medical, developmental, and psychological needs. Prognosis varies depending on the severity of symptoms and associated complications. | neurofibromin 1 | SH-SY5Y - Human neuroblastoma cells. SK-N-SH - Human neuroblastoma cells. PC12 - Rat pheochromocytoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | |
| 5 | 17q12 microdeletion syndrome renal cysts and diabetes (RCAD) syndrome or renal cysts and diabetes syndrome | The prevalence of renal cysts and diabetes (RCAD) syndrome is estimated to be relatively low, with reported rates varying among different populations. Studies have suggested that RCAD syndrome accounts for a small percentage of cases of early-onset diabetes and renal cystic diseases | HNF1B;LHX1 | Hepatocyte nuclear factor 1-beta Transcription factor 2 TCF-2 MODY5 (Maturity-Onset Diabetes of the Young 5) gene | Renal cysts and diabetes (RCAD) syndrome, also known as renal cysts and diabetes syndrome, is a genetic disorder characterized by the presence of renal cysts, early-onset diabetes, and, in some cases, other renal and extrarenal manifestations. It is caused by mutations in the HNF1B gene. Diagnosis is confirmed through genetic testing. The syndrome can be inherited in an autosomal dominant pattern. Management involves monitoring and treating diabetes and renal issues, and regular follow-up with a multidisciplinary team. Prognosis varies based on the severity of renal and diabetic complications, but early detection and management can improve outcomes | HNF1 homeobox B;LIM homeobox 1 | HepG2 (hepatocellular carcinoma cells). HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). NRK-52E (Normal Rat Kidney cells). BRL-3A (rat liver cells). RIN-m5F (rat insulinoma cells). | |
| 6 | 22q11.2 deletion syndrome DiGeorge syndrome, velocardiofacial syndrome (VCFS), or conotruncal anomaly face syndrome | 1 in 4,000 live births, making it one of the most common chromosomal microdeletion syndromes | ARVCF;JMJD1C;UFD1;COMT;TBX1;HIRA;GP1BB;RREB1;SEC24C | ARVCF: Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome. JMJD1C: Jumonji domain containing 1C. UFD1: Ubiquitin fusion degradation protein 1 homolog. COMT: Catechol-O-methyltransferase. TBX1: T-box transcription factor TBX1. HIRA: Histone cell cycle regulation-defective homolog A. GP1BB: Glycoprotein Ib platelet beta subunit. RREB1: Ras-responsive element-binding protein 1. SEC24C: SEC24 homolog C, COPII coat complex component | 22q11.2 deletion syndrome, also known as DiGeorge syndrome or velocardiofacial syndrome, is a genetic disorder caused by a deletion of a small segment on chromosome 22 at the q11.2 region. This syndrome presents with a wide range of symptoms, including congenital heart defects, characteristic facial features, developmental delays, intellectual disability, immune system deficiencies, and palate abnormalities. Other potential features include hearing loss, feeding difficulties, and psychiatric disorders such as schizophrenia. Diagnosis is typically made through genetic testing, and management involves a multidisciplinary approach to address the various medical, developmental, and psychological needs of affected individuals. Prognosis varies widely depending on the severity of symptoms and the presence of associated complications. | ARVCF delta catenin family member;jumonji domain containing 1C;ubiquitin recognition factor in ER associated degradation 1;catechol-O-methyltransferase;T-box transcription factor 1;histone cell cycle regulator;glycoprotein Ib platelet subunit beta;ras responsive element binding protein 1;SEC24 homolog C, COPII coat complex component | N2A (Neuro-2a) - Mouse neuroblastoma cells. SH-SY5Y - Human neuroblastoma cells. PC-3 - Human prostate cancer cells. | |
| 7 | 2q23.1 microdeletion syndrome Albright hereditary osteodystrophy-like syndrome | The prevalence of 2q23.1 microdeletion syndrome is not precisely known due to its rarity | MBD5 | KIAA1461 MGC129648 Protein containing methyl-CpG-binding domain 5 | 2q23.1 microdeletion syndrome is a rare genetic disorder characterized by the deletion of a segment on chromosome 2 at the q23.1 region. This syndrome presents with a spectrum of clinical features including developmental delays, intellectual disability, speech and motor impairments, growth abnormalities, distinctive facial features, and congenital malformations such as heart defects and skeletal anomalies. Diagnosis is typically confirmed through genetic testing, particularly chromosomal microarray analysis. Management involves a multidisciplinary approach to address medical, developmental, and behavioral issues | methyl-CpG binding domain protein 5 | SH-SY5Y - Human neuroblastoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. PC12 - Rat pheochromocytoma cells. | |
| 8 | 3-methylcrotonyl-CoA carboxylase deficiency MCC deficiency or 3-MCC deficiency | 1 in 50,000 to 1 in 150,000 newborns worldwid | MCCC1;MCCC2 | MCCC1: 3-Methylcrotonoyl-CoA carboxylase 1 3MCC1 Methylcrotonyl-CoA carboxylase subunit alpha MCCC2: 3-Methylcrotonoyl-CoA carboxylase 2 3MCC2 Methylcrotonyl-CoA carboxylase subunit beta | 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCC deficiency) is a rare inherited metabolic disorder characterized by the body's inability to break down the amino acid leucine properly. This condition is caused by mutations in the MCCC1 or MCCC2 genes, which encode the subunits of the enzyme 3-methylcrotonyl-CoA carboxylase. As a result, toxic byproducts accumulate in the body, leading to symptoms such as recurrent episodes of metabolic decompensation, including vomiting, dehydration, lethargy, and neurological abnormalities. Diagnosis is typically made through biochemical testing, including blood and urine tests, and confirmed by genetic testing. Management involves a low-protein diet, supplementation with carnitine and other nutrients, and prompt treatment of metabolic crises with intravenous fluids and glucose. With early detection and appropriate management, individuals with 3-MCC deficiency can lead relatively normal lives, although they may still be at risk for metabolic crises during periods of illness or stress. | methylcrotonyl-CoA carboxylase subunit 1;methylcrotonyl-CoA carboxylase subunit 2 | SH-SY5Y - Human neuroblastoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. C2C12 - Mouse myoblast cells. | |
| 9 | 3M syndrome Miller-McKusick-Malvaux syndrome | less than 1 in 1,000,000 individuals | OBSL1;CUL7;CCDC8 | OBSL1: Obscurin-like 1 hObs KIAA0896 CUL7: Cullin 7 Cullin-7 CUL-7 CCDC8: Coiled-Coil Domain Containing 8 Coiled-coil domain-containing protein 8 FLJ10781 | Miller-McKusick-Malvaux syndrome, also known as Carpenter-Waziri syndrome, is a rare genetic disorder characterized by intellectual disability, craniofacial abnormalities, skeletal anomalies, and other developmental abnormalities. It is caused by mutations in the IFT80 gene, which plays a role in intraflagellar transport and ciliogenesis. Common features include microcephaly, brachydactyly, syndactyly, and distinctive facial features such as a broad nasal bridge and prominent forehead. Diagnosis is typically made based on clinical presentation and confirmed through genetic testing. Management involves multidisciplinary care to address the various medical and developmental needs of affected individuals | obscurin like cytoskeletal adaptor 1;cullin 7;coiled-coil domain containing 8 | SH-SY5Y - Human neuroblastoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. THP-1 - Human monocytic cells. C2C12 - Mouse myoblast cells. L6 - Rat myoblast cells. | |
| 10 | 46,XX testicular disorder of sex development Swyer syndrome | approximately 1 in 20,000 to 1 in 90,000 live births | NR0B1;SRY;NR5A1;SOX9;SOX3 | NR0B1: DAX1 (Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) Adrenal hypoplasia congenita critical region on chromosome X, gene 1 AHCH AHC DSS SRY: Sex-determining region Y Testis-determining factor TDY NR5A1: Steroidogenic factor 1 SF-1 Adrenal 4-binding protein Ad4BP SOX9: SRY-box transcription factor 9 Campomelic dysplasia autosomal sex reversal CMD1 SRA1 SOX3: SRY-box transcription factor 3 LXP SRY-related HMG-box gene 3 | 46,XX testicular disorder of sex development (DSD), also known as XX male syndrome, is a rare condition where individuals with a 46,XX karyotype typically associated with females develop testes instead of ovaries. Despite having the typical male gonads, affected individuals may exhibit external genitalia that appear female or ambiguous. This condition is often caused by mutations in genes involved in sex determination and differentiation pathways. Diagnosis involves genetic testing and evaluation of reproductive anatomy. Management may include hormone replacement therapy and surgical interventions to align gender identity with physical characteristics | nuclear receptor subfamily 0 group B member 1;sex determining region Y;nuclear receptor subfamily 5 group A member 1;SRY-box transcription factor 9;SRY-box transcription factor 3 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). R2C (Leydig tumor cells). PC12 (pheochromocytoma cells). BRL-3A (rat liver cells) | |
| 11 | 46,XY complete gonadal dysgenesis Swyer syndrome | estimated to be around 1 in 150,000 to 1 in 200,000 live births | WT1;CBX2;DHX37;DHH;DMRT1;NR5A1;NR0B1;MAP3K1;SOX9;SRY | WT1: Wilms tumor 1 WAGR WIT-2 NPHS4 CBX2: Chromobox 2 HP1-beta HP1Hsbeta DHX37: DEAH-box helicase 37 DDX37 DHH: Desert hedgehog homolog DHHB HPE3 DMRT1: Doublesex- and mab-3-related transcription factor 1 Dmrt7 DMRTA1 NR5A1: Nuclear receptor subfamily 5 group A member 1 SF-1 Adrenal 4-binding protein Ad4BP FTZ-F1 SF1 NR0B1: Nuclear receptor subfamily 0 group B member 1 DAX1 AHCH MAP3K1: Mitogen-activated protein kinase kinase kinase 1 MEKK1 MAPKKK1 SOX9: SRY-box transcription factor 9 CMD1 SRA1 SRY: Sex-determining region Y TDY | 46,XY complete gonadal dysgenesis is a rare genetic disorder characterized by individuals with a male chromosomal pattern (46,XY) who have underdeveloped or absent gonads, resulting in incomplete or absent development of male reproductive structures. This condition typically presents with ambiguous genitalia at birth and is often associated with primary amenorrhea in affected individuals assigned female at birth. It is caused by mutations in genes involved in the development of the gonads, such as SRY or other genes on the Y chromosome, leading to gonadal dysgenesis. Diagnosis is confirmed through genetic testing and imaging studies. Management involves hormone replacement therapy to induce secondary sexual characteristics and address potential complications such as osteoporosis | WT1 transcription factor;chromobox 2;DEAH-box helicase 37;desert hedgehog signaling molecule;doublesex and mab-3 related transcription factor 1;nuclear receptor subfamily 5 group A member 1;nuclear receptor subfamily 0 group B member 1;mitogen-activated protein kinase kinase kinase 1;SRY-box transcription factor 9;sex determining region Y | A549 - Human lung carcinoma cells. NIH 3T3 - Mouse fibroblast cells. | |
| 12 | 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency 5-alpha-reductase deficiency or simply 5-ARD | estimated to be approximately 1 in 130,000 to 1 in 150,000 births worldwide | SRD5A2 | SRD5A2: Steroid 5-alpha-reductase 2 5-ARD 5-alpha reductase type 2 | 5-alpha-reductase deficiency (5-ARD) is a genetic condition characterized by the impaired function of the enzyme 5-alpha-reductase, which is responsible for converting testosterone into dihydrotestosterone (DHT). This deficiency leads to a disruption in the development of male sex characteristics in individuals assigned male at birth. Common features include ambiguous genitalia at birth, varying degrees of virilization during puberty, and infertility in individuals with severe forms of the condition. Diagnosis is typically made through hormone testing and genetic analysis. Management may involve hormone replacement therapy and surgical interventions to address genital ambiguity. With appropriate treatment, individuals with 5-ARD can lead healthy lives | steroid 5 alpha-reductase 2 | PC-3 - Human prostate cancer cells. HepG2 - Human liver carcinoma cells. HaCaT - Immortalized human keratinocyte cells. | |
| 13 | 46,xy sex reversal 2 Testicular Regression Syndrome or TRS | approximately 1 in 20,000 to 1 in 30,000 live births | NR0B1 | DAX1 (Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) Adrenal hypoplasia congenita critical region on chromosome X, gene 1 AHCH AHC DSS | 46,XY sex reversal 2, also known as SRXY2, is a genetic disorder characterized by individuals with a 46,XY karyotype (typically associated with males) who develop characteristics typical of females. This condition is caused by mutations in certain genes involved in sex determination and differentiation, leading to incomplete or ambiguous development of the external genitalia. Individuals with SRXY2 may have varying degrees of undervirilization, ranging from mild genital ambiguity to complete female external genitalia. Diagnosis is typically made through genetic testing to identify mutations in genes such as NR5A1 or MAP3K1. Management involves a multidisciplinary approach with medical and psychological support, and treatment may include hormone therapy and surgical interventions to align physical appearance with gender identity. Prognosis depends on the specific genetic and anatomical features of each individual | nuclear receptor subfamily 0 group B member 1 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). R2C (Leydig tumor cells). PC12 (pheochromocytoma cells). BRL-3A (rat liver cells) | |
| 14 | Abetalipoproteinemia Bassen-Kornzweig syndrome | approximately 1 in 1,000,000 individuals worldwide | MTTP | Microsomal triglyceride transfer protein MTP MTTP | Abetalipoproteinemia is a rare genetic disorder characterized by the body's inability to properly absorb dietary fats, cholesterol, and fat-soluble vitamins. It is caused by mutations in the microsomal triglyceride transfer protein (MTTP) gene, which plays a crucial role in the assembly and secretion of lipoproteins. Common symptoms include fat malabsorption leading to steatorrhea (excessive fat in feces), failure to thrive, neurological abnormalities, and vision problems due to vitamin deficiencies. Diagnosis is often based on clinical symptoms, lipid profiles, and genetic testing. Treatment typically involves lifelong dietary modifications, supplementation with fat-soluble vitamins, and management of associated complications | microsomal triglyceride transfer protein | HepG2 - Human liver carcinoma cells. HT-29 - Human colorectal adenocarcinoma cells. HEK293 - Human embryonic kidney cells (often used in transfection studies, including those involving MTTP). | |
| 15 | Acheiropodia Limb-Body Wall Complex | 1 in 10 million births worldwide | LMBR1 | Limb region 1 homolog LIMR Limb development membrane protein 1 | Acheiropodia is an extremely rare genetic disorder characterized by the absence of hands and feet at birth. Affected individuals typically have well-formed forearms and lower legs that end abruptly, often described as "flippers." This condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected. While the exact genetic cause is not fully understood, mutations in the LMBR1 gene have been implicated in some cases | limb development membrane protein 1 | HEK293 (human embryonic kidney cells). HeLa (cervical cancer cells). A549 (lung carcinoma cells). PC12 (pheochromocytoma cells). RBL-2H3 (rat basophilic leukemia cells). NRK-52E (Normal Rat Kidney cells). | |
| 16 | Acquired idiopathic sideroblastic anemia primary acquired sideroblastic anemia (PASA) | 1 to 2 cases per 100,000 individuals in the general population | SF3B1;TET2 | SF3B1: Splicing factor 3B subunit 1 SAP155 (SR-related protein associated with the spliceosome) SF3B155 TET2: Tet methylcytosine dioxygenase 2 Jumonji domain-containing protein D2 LCX (leukemia-associated protein with a CXXC domain) KIAA1546 | Acquired idiopathic sideroblastic anemia (AISA) is a type of anemia characterized by the presence of ringed sideroblasts in the bone marrow, which are erythroblasts with abnormal iron accumulation. Unlike hereditary forms of sideroblastic anemia, the acquired form has no known underlying genetic cause and is typically seen in adults. Common symptoms include fatigue, weakness, pallor, and shortness of breath. Diagnosis involves blood tests, bone marrow examination, and ruling out other causes of anemia. Treatment options may include iron chelation therapy, erythropoiesis-stimulating agents, and blood transfusions, depending on the severity of symptoms and underlying factors | splicing factor 3b subunit 1;tet methylcytosine dioxygenase 2 | HeLa (cervical cancer cells). HEK293 (human embryonic kidney cells). A549 (lung carcinoma cells). PC12 (pheochromocytoma cells). NRK-52E (Normal Rat Kidney cells). BRL-3A (rat liver cells). | |
| 17 | Acquired partial lipodystrophy Barraquer-Simons syndrome | 1–9 in 100,000 population | LMNB2 | Lamin B2 | Barraquer-Simons syndrome, also known as lipodystrophy acquired partial, is a rare disorder characterized by the selective loss of subcutaneous fat, leading to a lean appearance with prominent veins and muscles. Individuals with this syndrome may experience metabolic abnormalities such as insulin resistance, hypertriglyceridemia, and liver steatosis. The exact cause of Barraquer-Simons syndrome is not fully understood, but it is thought to involve a combination of genetic and environmental factors. Treatment focuses on managing associated metabolic complications and may include lifestyle modifications, medications, and monitoring for potential complications such as diabetes and cardiovascular disease | lamin B2 | N2A (Neuro-2a) - Mouse neuroblastoma cells. THP-1 - Human monocytic cells. HeLa - Human cervical cancer cells. PC-3 - Human prostate cancer cells. | |
| 18 | Acrocallosal syndrome Schinzel syndrome | 1 in 1 million individuals | GLI3;KIF7 | Kinesin family member 7 KIAA1456 | Acrocallosal syndrome is a rare genetic disorder characterized by a combination of physical, neurological, and developmental abnormalities. It is typically caused by mutations in the KIF7 gene. Common features include craniofacial anomalies such as a prominent forehead, widely spaced eyes, and a flat nasal bridge, as well as limb malformations like extra fingers or toes (polydactyly). Individuals with acrocallosal syndrome may also have intellectual disability, delays in motor skills development, and structural brain abnormalities including absence or underdevelopment of the corpus callosum, which connects the brain's hemispheres. Management typically involves addressing medical and developmental needs through a multidisciplinary approach, including surgical interventions for limb anomalies and supportive therapies for developmental delays. Prognosis varies depending on the severity of symptoms, but with appropriate care, many individuals with acrocallosal syndrome can lead fulfilling lives. | GLI family zinc finger 3;kinesin family member 7 | ||
| 19 | Acrodysostosis Maroteaux-Malamut syndrome | it affects fewer than 1 in 1 million people worldwide | PDE4D;PRKAR1A | PDE4D: Phosphodiesterase 4D DPDE3 DPDE3A PRKAR1A: cAMP-dependent protein kinase type I-alpha regulatory subunit PKR1 TSE1 | Acrodysostosis is a rare genetic disorder characterized by skeletal abnormalities, including shortened bones in the hands and feet, facial dysostosis, and nasal hypoplasia. It often presents with short stature, intellectual disability, and hormone resistance, particularly to parathyroid and thyroid hormones. The condition is typically caused by mutations in the PRKAR1A or PDE4D genes, which affect bone development and hormone signaling pathways. Diagnosis is based on clinical features, radiographic findings, and genetic testing | phosphodiesterase 4D;protein kinase cAMP-dependent type I regulatory subunit alpha | ||
| 20 | Acrofacial dysostosis, Weyers type Weyers acrodental dysostosis | Only a few affected families have been identified worldwide | EVC;EVC2 | Ellis-van Creveld syndrome protein Ellis-van Creveld syndrome 2 protein | Acrofacial dysostosis, Weyers type (WAD), is a rare genetic disorder characterized by abnormalities in the development of the bones of the face and limbs. Key features include: Short stature and short limbs (especially the lower legs and forearms). Dental anomalies, such as extra teeth (supernumerary teeth) and dental crowding. Nail dysplasia, often presenting as small or missing nails. Facial abnormalities, including a prominent forehead, small jaw (micrognathia), and sometimes a cleft palate. WAD is caused by mutations in the EVC or EVC2 genes and is inherited in an autosomal dominant pattern. The condition is part of a spectrum of disorders known as Ellis-van Creveld syndrome, with Weyers type being the milder form. | EvC ciliary complex subunit 1;EvC ciliary complex subunit 2 | ||
| 21 | Acrogeria Gottron syndrome | fewer than 50 reported cases in the medical literature worldwide | COL3A1 | Collagen type III alpha 1 chain EDS4A (Ehlers-Danlos syndrome type IV, autosomal dominant) Collagen III FLJ34534 | Acrogeria, also known as Gottron's syndrome, is a rare genetic disorder characterized by premature aging of the skin, primarily affecting the extremities such as the hands and feet. Individuals with this condition exhibit thin, wrinkled, and translucent skin, which makes their veins more prominent. The disorder also leads to a significant reduction in subcutaneous fat, contributing to the aged appearance of the affected areas. Joint abnormalities, including stiffness or deformities, may also be present. Acrogeria typically manifests in early childhood and progresses over time. It is usually inherited in an autosomal dominant pattern, though sporadic cases can occur. Currently, there is no cure for acrogeria, and treatment mainly focuses on managing symptoms and protecting the delicate skin. | collagen type III alpha 1 chain | ||
| 22 | Acromegaly Gigantism | about 40 to 60 cases per million people | GPR101;AIP | GPR101: G-protein coupled receptor 101 GPCR6 AIP: Aryl hydrocarbon receptor-interacting protein AIP1 AH receptor-interacting protein XAP2 (X-associated protein 2) ARA9 (AIP-related protein) | Acromegaly is a rare hormonal disorder that results from the overproduction of growth hormone (GH) by the pituitary gland, usually due to a benign tumor called a pituitary adenoma. This excess GH leads to the enlargement of bones and tissues, most notably in the hands, feet, and face. Symptoms include enlarged hands and feet, facial changes like protruding jaw and brow, thickened skin, and joint pain. Over time, acromegaly can cause serious health issues such as diabetes, hypertension, cardiovascular disease, and arthritis. Early diagnosis and treatment, typically involving surgery, medication, or radiation therapy, are crucial to managing the condition and preventing complications. | G protein-coupled receptor 101;aryl hydrocarbon receptor interacting protein | PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. NIH 3T3 - Mouse fibroblast cells. BJ - Human foreskin fibroblast cells. | |
| 23 | Acromicric dysplasia Geleophysic dysplasia type 2 | fewer than 1 in 1,000,000 individuals worldwide | LTBP3;FBN1 | LTBP3: Latent transforming growth factor beta binding protein 3 LTBP-3 FBN1: Fibrillin 1 Marfan syndrome 1 MFS1 | Acromicric dysplasia is a rare genetic disorder characterized by skeletal abnormalities, short stature, distinctive facial features, and joint limitations. Individuals with acromicric dysplasia typically have short hands and feet with characteristic stubby fingers and toes, as well as a short stature relative to their peers. Facial features may include a round face with prominent cheeks, a small nose, and a relatively flat nasal bridge. Joint limitations, particularly in the hands and feet, can lead to difficulties with mobility and fine motor skills. This condition is caused by mutations in the FBN1 gene, which encodes a protein involved in the formation of connective tissue. While there is no cure for acromicric dysplasia, management typically focuses on addressing symptoms and improving quality of life through supportive care and interventions tailored to individual needs | latent transforming growth factor beta binding protein 3;fibrillin 1 | NIH 3T3 - Mouse fibroblast cells. A549 - Human lung carcinoma cells. HeLa - Human cervical cancer cells. | |
| 24 | Activated PI3K-delta syndrome PI3KDelta-Activated Syndrome with Immunodeficiency | 1-2 affected people per million | PIK3CD;PTEN;PIK3R1 | PIK3CD: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PI3Kδ PI3K-p110δ p110δ PTEN: Phosphatase and tensin homolog MMAC1 (Mutated in multiple advanced cancers 1) TEP1 (TGF-beta-regulated and epithelial cell-enriched phosphatase 1) PIK3R1: Phosphoinositide-3-kinase regulatory subunit 1 PI3K p85α GRB1 (Growth factor receptor-bound protein 1) p85α p55α p50α | Activated PI3K-delta syndrome (APDS) is a rare primary immunodeficiency disorder caused by gain-of-function mutations in the PIK3CD gene, leading to dysregulation of the phosphoinositide 3-kinase (PI3K) signaling pathway. This dysregulation results in hyperactivation of PI3K-delta, affecting various immune cell functions such as B cell development, T cell activation, and innate immune responses. Clinically, APDS is characterized by recurrent respiratory infections, lymphoproliferation, autoimmunity, and increased susceptibility to certain infections, particularly caused by encapsulated bacteria. Management typically involves immunoglobulin replacement therapy, antimicrobial prophylaxis, and, in some cases, targeted therapies aimed at modulating the PI3K pathway. Early diagnosis and appropriate management are crucial for optimizing outcomes in individuals with APDS. | phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta;phosphatase and tensin homolog;phosphoinositide-3-kinase regulatory subunit 1 | ||
| 25 | Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) Acute Myeloid Leukemia with inv(16) | it represents approximately 5-8% of all AML cases | CBFB;FLT3;MYH11;KIT | CBFB: Core-binding factor beta PEBP2B (polyomavirus enhancer-binding protein 2, beta subunit) FLT3: FMS-like tyrosine kinase 3 CD135 FLK2 (Fetal liver kinase-2) STK1 (Stem cell tyrosine kinase 1) MYH11: Myosin heavy chain 11 AAT4 FAA4 SMHCA (Smooth muscle heavy chain A) KIT: KIT proto-oncogene receptor tyrosine kinase CD117 C-KIT SCFR (Stem cell factor receptor) | Acute Myeloid Leukemia (AML) with inv(16), also known as AML with core-binding factor (CBF) rearrangement, represents a subtype of AML characterized by a distinct genetic abnormality involving the inversion of chromosome 16. This inversion leads to the fusion of two genes: CBFB and MYH11, resulting in the formation of the CBFB-MYH11 fusion gene. Clinically, patients with AML inv(16) typically present with features such as eosinophilia, thrombocytopenia, and a favorable prognosis compared to other AML subtypes. The CBFB-MYH11 fusion protein disrupts normal hematopoietic differentiation by interfering with transcriptional regulation, ultimately contributing to leukemogenesis. Treatment for AML inv(16) often involves intensive chemotherapy regimens, with some patients also benefiting from allogeneic stem cell transplantation for consolidation therapy. Overall, AML with inv(16) represents a distinct molecular subtype of AML with its own clinical and therapeutic implications. | core-binding factor subunit beta;fms related receptor tyrosine kinase 3;myosin heavy chain 11;KIT proto-oncogene, receptor tyrosine kinase | ||
| 26 | Acute promyelocytic leukemia M3 acute myeloid leukemia (M3-AML) | IRF2BP2;BCOR;STAT5B;STAT3;PRKAR1A;RARA;FIP1L1;NABP1;TBL1XR1;NPM1;ZBTB16;NUMA1;PML | IRF2BP2: Interferon regulatory factor 2 binding protein 2 IRF2BP2 BCOR: BCL6 corepressor BCL6 interacting corepressor KIAA1575 STAT5B: Signal transducer and activator of transcription 5B STAT5B STAT3: Signal transducer and activator of transcription 3 STAT3 PRKAR1A: Protein kinase cAMP-dependent type I regulatory subunit alpha PRKAR1A RARA: Retinoic acid receptor alpha RARA FIP1L1: Factor interacting with PAPOLA and CPSF1 FIP1L1 NABP1: Nucleic acid binding protein 1 NABP1 TBL1XR1: Transducin beta-like 1 X-linked receptor 1 TBL1XR1 NPM1: Nucleophosmin 1 NPM1 ZBTB16: Zinc finger and BTB domain containing 16 ZBTB16 NUMA1: Nuclear mitotic apparatus protein 1 NUMA1 PML: Promyelocytic leukemia protein PML | Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by the abnormal accumulation of immature promyelocytes in the bone marrow and blood. It is distinguished by a specific chromosomal translocation, t(15;17), which results in the fusion of the promyelocytic leukemia (PML) gene on chromosome 15 with the retinoic acid receptor-alpha (RARα) gene on chromosome 17. This fusion leads to impaired differentiation and increased proliferation of promyelocytes. A hallmark of APL is its high sensitivity to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which induce differentiation and apoptosis of leukemic cells, respectively, resulting in high rates of complete remission and overall survival. However, APL is also associated with a risk of life-threatening coagulopathy, necessitating prompt diagnosis and specialized management strategies. | interferon regulatory factor 2 binding protein 2;BCL6 corepressor;signal transducer and activator of transcription 5B;signal transducer and activator of transcription 3;protein kinase cAMP-dependent type I regulatory subunit alpha;retinoic acid receptor alpha;factor interacting with PAPOLA and CPSF1;nucleic acid binding protein 1;TBL1X receptor 1;nucleophosmin 1;zinc finger and BTB domain containing 16;nuclear mitotic apparatus protein 1;PML nuclear body scaffold | |||
| 27 | Adams-Oliver syndrome Congenital scalp defects with terminal limb anomalies | fewer than 1 in 100,000 individuals affected worldwide | EOGT;DOCK6;ARHGAP31;NOTCH1;DLL4;RBPJ | EOGT: EGF domain-specific O-linked N-acetylglucosamine transferase EOGT1 EOGT2 EOGT3 DOCK6: Dedicator of cytokinesis protein 6 ZIR2 (Zinc finger protein regulated in stress) Zizimin2 FLJ21063 ARHGAP31: Rho GTPase-activating protein 31 RhoGAP36 FLJ10489 NOTCH1: Neurogenic locus notch homolog protein 1 TAN1 (Translocation-associated notch homolog 1) hN1 NOTCH DLL4: Delta-like protein 4 Delta4 RBPJ: Recombining binding protein suppressor of hairless CSL (C promoter-binding factor 1, Suppressor of hairless, Lag-1) RBPJK | Adams-Oliver syndrome (AOS) is a rare genetic disorder characterized by the combination of congenital scalp defects, often manifesting as missing patches of skin or abnormalities of the skull bones, and malformations of the limbs, such as absent or underdeveloped fingers or toes. Additional features may include cardiovascular abnormalities, such as heart defects or blood vessel abnormalities, as well as neurological complications. AOS is typically caused by mutations in genes involved in vascular development, leading to impaired blood vessel formation during embryonic development. The severity of AOS can vary widely among affected individuals, ranging from mild to severe manifestations. Treatment primarily focuses on addressing specific symptoms and may involve surgical interventions to correct limb or scalp defects, as well as management of associated health issues. | EGF domain specific O-linked N-acetylglucosamine transferase;dedicator of cytokinesis 6;Rho GTPase activating protein 31;notch receptor 1;delta like canonical Notch ligand 4;recombination signal binding protein for immunoglobulin kappa J region | NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. HeLa - Human cervical cancer cells. PC-3 - Human prostate cancer cells. | |
| 28 | Adrenocortical carcinoma Adrenal cortex carcinoma | 0.5 to 2 cases per million individuals per year | TP53 | Tumor protein p53 p53 Transformation-related protein 53 Antigen NY-CO-13 | Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy arising from the adrenal cortex, typically presenting with hormonal dysregulation and/or symptoms related to tumor growth. It accounts for only a small fraction of adrenal tumors, with an annual incidence of 0.5-2 cases per million individuals. ACC commonly manifests with symptoms such as abdominal pain, weight loss, and hormonal imbalances due to excessive production of adrenal hormones, including cortisol, aldosterone, and androgens. Diagnosis often involves imaging studies like CT or MRI, along with hormonal assays and biopsy confirmation. Treatment options vary based on the tumor stage but may include surgery, chemotherapy, and targeted therapies, with prognosis heavily dependent on the disease stage at diagnosis and the effectiveness of treatment interventions. | tumor protein p53 | ||
| 29 | Adrenomyeloneuropathy Addison disease, X-linked, with cerebral sclerosis | 1 in 20,000 to 1 in 40,000 individuals | ABCD1 | ATP-binding cassette sub-family D member 1 ALDP (Adrenoleukodystrophy protein) ALD protein ALDPX (Adrenoleukodystrophy protein X) | Adrenomyeloneuropathy (AMN) is a rare genetic disorder characterized by the progressive degeneration of the spinal cord, adrenal gland dysfunction, and peripheral neuropathy. It is a subtype of adrenoleukodystrophy (ALD), primarily affecting adult males, although females can also be affected. AMN typically presents with symptoms such as stiffness, weakness, and pain in the legs, as well as bladder and bowel dysfunction. Adrenal insufficiency, leading to hormonal imbalances, is another hallmark feature. The condition is caused by mutations in the ABCD1 gene, resulting in the accumulation of very long-chain fatty acids (VLCFAs) in various tissues, including the nervous system. While there is currently no cure for AMN, management strategies focus on symptom relief and supportive care, including hormone replacement therapy and physical therapy. Early detection through genetic testing and symptom monitoring is crucial for optimizing treatment outcomes and quality of life for affected individuals. | ATP binding cassette subfamily D member 1 | ||
| 30 | Adult hepatocellular carcinoma Hepatoma | 782,000 new cases annually, with over 746,000 deaths attributed to the disease each year | TSC1;EGF;CASP8;CTNNB1;PDGFRL;PIK3CA;TSC2;AXIN1;TP53 | TSC1: Tuberous sclerosis 1 Hamartin KIAA0243 EGF: Epidermal growth factor CASP8: Caspase 8 FLICE (FADD-like interleukin-1beta-converting enzyme) FLICE1 CTNNB1: Catenin beta-1 Beta-catenin CTNNB PDGFRL: Platelet-derived growth factor receptor-like protein MGC142159 PGR15 PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform p110α TSC2: Tuberous sclerosis 2 Tuberin AXIN1: Axis inhibition protein 1 Conductin AXIN PPP1R49 TP53: Tumor protein p53 p53 Transformation-related protein 53 Antigen NY-CO-13 | Adult hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, typically arising from hepatocytes, the main cell type in the liver. It is strongly associated with chronic liver diseases, notably cirrhosis caused by viral hepatitis (B and C), alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and aflatoxin exposure. Symptoms often manifest in later stages, including abdominal pain, weight loss, jaundice, and hepatomegaly. Diagnosis involves imaging studies like ultrasound, CT scans, and MRI, along with serum biomarkers such as alpha-fetoprotein (AFP). Treatment options depend on the stage of the cancer and may include surgical resection, liver transplantation, ablation therapy, transarterial chemoembolization (TACE), systemic chemotherapy, or targeted therapies such as sorafenib. Prognosis varies widely based on tumor stage, underlying liver function, and treatment response, with early detection significantly improving outcomes. | TSC complex subunit 1;epidermal growth factor;caspase 8;catenin beta 1;platelet derived growth factor receptor like;phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha;TSC complex subunit 2;axin 1;tumor protein p53 | ||
| 31 | Adult polyglucosan body disease | approximately 1 in 100,000 individuals | GBE1 | GBE 1,4-alpha-glucan-branching enzyme Amylo-(1,4 to 1,6) transglycosylase Branching enzyme 1 Glycogen Branching Enzyme | Adult polyglucosan body disease (APBD) is a rare neurodegenerative disorder characterized by the accumulation of polyglucosan bodies in the central and peripheral nervous systems. It typically manifests in adulthood, with symptoms including progressive weakness and stiffness in the legs, urinary urgency and incontinence, and sensory loss. Cognitive impairment may also occur in some cases. APBD is caused by mutations in the GBE1 gene, resulting in deficiency of the glycogen branching enzyme. This leads to the abnormal accumulation of glycogen in nerve cells, disrupting their function. Diagnosis often involves genetic testing and nerve biopsies, while management focuses on symptom relief and supportive care, as there is currently no cure for the disease. | 1,4-alpha-glucan branching enzyme 1 | ||
| 32 | Adult-onset autosomal dominant leukodystrophy | less than 1 in 1,000,000 individuals | LMNB1 | LMN2 Lamin B1 Lamin-B1 | Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare genetic disorder characterized by progressive degeneration of the white matter in the central nervous system, typically manifesting in adulthood. It is caused by duplications of the LMNB1 gene, leading to overexpression of lamin B1, a structural protein in the nuclear envelope. Symptoms often begin with autonomic dysfunction, such as urinary and bowel incontinence, followed by motor and cognitive impairments, including muscle stiffness, spasticity, and ataxia. ADLD progresses gradually, and while there is currently no cure, management focuses on alleviating symptoms and improving quality of life through supportive therapies | lamin B1 | ||
| 33 | AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome | fewer than 100 cases have been documented worldwide | AHDC1 | KIAA0529 AT-Hook DNA Binding Motif Containing 1 | AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome is a rare genetic disorder caused by mutations in the AHDC1 gene. This syndrome is characterized by intellectual disability, developmental delays, and distinctive facial features, which may include a broad forehead, wide-set eyes, and a flat nasal bridge. Affected individuals often experience obstructive sleep apnea due to craniofacial abnormalities and hypotonia. Additional features may include poor muscle tone, speech delays, and behavioral issues. Diagnosis is typically confirmed through genetic testing, and management focuses on addressing the individual symptoms, such as providing educational support, treating sleep apnea, and managing any other associated medical conditions. | AT-hook DNA binding motif containing 1 | ||
| 34 | Aicardi-Goutières syndrome | approximately 1 in 100,000 to 1 in 1,000,000 individuals globally | ADAR;TREX1;RNASEH2B;RNASEH2C;SAMHD1;RNASEH2A;IFIH1 | ADAR (Adenosine Deaminase, RNA-Specific) Alias: ADAR1 TREX1 (Three Prime Repair Exonuclease 1) Alias: DNT1, TREX1L, AGS1, Aicardi-Goutieres syndrome 1 protein RNASEH2B (Ribonuclease H2 Subunit B) Alias: RNase H(35 kD) subunit B, RNASEH35B, Aicardi-Goutieres syndrome 2 protein RNASEH2C (Ribonuclease H2 Subunit C) Alias: RNase H(30 kD) subunit C, RNASEH30C SAMHD1 (SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1) Alias: SAMHD1, Aicardi-Goutieres syndrome 5 protein RNASEH2A (Ribonuclease H2 Subunit A) Alias: RNase H(49 kD) subunit A, RNASEH49A IFIH1 (Interferon Induced with Helicase C Domain 1) Alias: MDA5, Helicard, Melanoma Differentiation-Associated protein 5 | Aicardi-Goutières syndrome (AGS) is a rare genetic disorder that predominantly affects the brain and skin, often presenting with symptoms similar to congenital viral infections. Typically manifesting in infancy or early childhood, AGS is characterized by progressive encephalopathy, leading to severe intellectual and physical disabilities. Patients may exhibit symptoms such as irritability, feeding difficulties, developmental regression, and spasticity. Other notable features include chronic cerebrospinal fluid lymphocytosis, intracranial calcifications, and elevated interferon-alpha levels. Mutations in any of several genes, including TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1, can cause AGS, and it is inherited in an autosomal recessive or, in rare cases, autosomal dominant manner. There is no cure, and treatment focuses on managing symptoms and supportive care. | adenosine deaminase RNA specific;three prime repair exonuclease 1;ribonuclease H2 subunit B;ribonuclease H2 subunit C;SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1;ribonuclease H2 subunit A;interferon induced with helicase C domain 1 | ||
| 35 | ALG1-CDG | only a few dozen cases reported worldwide | ALG1 | ALG1, Chitobiosyldiphosphodolichol Beta-Mannosyltransferase CDG1K (Congenital disorder of glycosylation, type Ik) DPMS (Dolichyl-phosphate beta-D-mannosyltransferase) GPT14 (Glycosylphosphatidylinositol-anchored protein 14) MRT5 (Mannosyltransferase 5) ALG1, Chitobiosyldiphosphodolichol Beta-Mannosyltransferase Homolog (S. Cerevisiae) | ALG1-CDG, or ALG1 congenital disorder of glycosylation, is a rare genetic disorder characterized by deficiencies in the ALG1 gene, which is responsible for producing an enzyme involved in the process of protein glycosylation. This deficiency leads to abnormalities in glycoprotein synthesis, impacting various bodily functions. Individuals with ALG1-CDG may experience a range of symptoms, including developmental delay, intellectual disability, seizures, liver dysfunction, and abnormalities in facial features. The severity of the condition can vary widely among affected individuals, with some experiencing life-threatening complications. Management typically involves supportive care and may include therapies aimed at addressing specific symptoms. Early diagnosis through genetic testing is crucial for implementing appropriate interventions and improving outcomes for affected individuals. | ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase | HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | |
| 36 | ALG9-CDG | approximately 1 in 20,000 to 1 in 100,000 live births | ALG9 | DPMS2 MRT11 ALG9, alpha-1,2-mannosyltransferase Alpha-1,2-mannosyltransferase ALG9 | ALG9-CDG, also known as congenital disorder of glycosylation (CDG) caused by mutations in the ALG9 gene, is a rare genetic disorder affecting the process of protein glycosylation. ALG9 encodes an enzyme involved in the early steps of N-linked glycosylation, a crucial process for proper protein folding and function. Defects in ALG9 lead to impaired glycosylation, resulting in a spectrum of clinical manifestations including developmental delay, intellectual disability, seizures, growth retardation, and various organ dysfunctions. Symptoms can vary widely in severity, and diagnosis often involves genetic testing and biochemical analysis of glycosylation patterns. Management typically focuses on supportive care and may include physical and occupational therapy, dietary modifications, and treatment of specific symptoms. | ALG9 alpha-1,2-mannosyltransferase | ||
| 37 | Alopecia universalis | 1 in 100,000 individuals | HR | BRCA1 (Breast Cancer Type 1 Susceptibility Protein) BRCA2 (Breast Cancer Type 2 Susceptibility Protein) RAD51 (RAD51 Recombinase) RAD52 (RAD52 Homolog, DNA Repair Protein) RAD54 (RAD54 Homolog, DNA Repair Protein) RAD51C (RAD51 Paralog C) RAD51D (RAD51 Paralog D) RAD51B (RAD51 Paralog B) RAD51AP1 (RAD51 Associated Protein 1) PALB2 (Partner and Localizer of BRCA2) XRCC2 (X-ray Repair Cross Complementing 2) XRCC3 (X-ray Repair Cross Complementing 3) | Alopecia universalis is a severe form of alopecia areata, an autoimmune disorder characterized by sudden and complete hair loss across the entire body, including the scalp, eyebrows, eyelashes, and body hair. Unlike alopecia areata, which typically presents with patchy hair loss, alopecia universalis results in the total absence of hair, leaving the affected individual completely bald. This condition is thought to occur when the immune system mistakenly targets hair follicles, leading to their destruction and subsequent hair loss. Alopecia universalis can have a significant impact on a person's physical appearance and emotional well-being, as it can cause distress and impact self-esteem. Treatment options for alopecia universalis are limited, and while some individuals may experience spontaneous hair regrowth, others may require ongoing management with therapies such as corticosteroids, immunosuppressants, or topical treatments to help stimulate hair regrowth. | HR lysine demethylase and nuclear receptor corepressor | NIH 3T3 - Mouse fibroblast cells. HeLa - Human cervical cancer cells. HEK293 - Human embryonic kidney cells. | |
| 38 | Alopecia-intellectual disability syndrome | only a few reported cases worldwide | LSS;AHSG;ITGB6 | LSS (Lanosterol Synthase) Alias: LPC, CYP51 AHSG (Alpha-2-HS-Glycoprotein) Alias: Fetuin-A, FETUA, Alpha-2-Z-globulin, Gp-40, BFGF-R3 ITGB6 (Integrin Subunit Beta 6) Alias: Integrin beta-6, CD49f, ITGbeta6 | Alopecia-intellectual disability syndrome, also known as Marie Unna hereditary hypotrichosis, is a rare genetic disorder characterized by early-onset hair loss (alopecia) and intellectual disability. This syndrome typically presents with sparse or absent scalp hair, as well as abnormalities in hair growth on other parts of the body. Alongside alopecia, individuals with this condition often exhibit developmental delays, intellectual disability, and in some cases, additional physical abnormalities. The syndrome is inherited in an autosomal recessive pattern, meaning both copies of the responsible gene must be mutated for the condition to manifest. Treatment primarily focuses on managing symptoms and providing support for developmental and intellectual challenges. | lanosterol synthase;alpha 2-HS glycoprotein;integrin subunit beta 6 | NIH 3T3 - Mouse fibroblast cells. HeLa - Human cervical cancer cells. HEK293 - Human embryonic kidney cells. PC-3 - Human prostate cancer cells. | |
| 39 | Alpers-Huttenlocher syndrome | 1 in 100,000 to 1 in 250,000 individuals affected | POLG | POLG1: This is the main isoform of the POLG gene. MTPOLG: Mitochondrial DNA-directed DNA polymerase gamma. POLGA: Polymerase (DNA directed), gamma, A. | Alpers-Huttenlocher syndrome (AHS) is a rare and severe neurological disorder primarily affecting infants and young children. It is characterized by a triad of symptoms including intractable seizures, developmental regression, and liver dysfunction. The syndrome is typically caused by mutations in the POLG gene, which encodes a mitochondrial DNA polymerase involved in replication and repair processes. As a result, affected individuals experience progressive neurological deterioration, leading to profound developmental delays and often early mortality. The liver dysfunction observed in AHS can manifest as hepatomegaly, liver failure, or elevated liver enzymes. Early diagnosis and management are crucial, although treatment options remain limited, focusing primarily on supportive care and symptom management. | DNA polymerase gamma, catalytic subunit | ||
| 40 | Alpha-thalassemia-X-linked intellectual disability syndrome | fewer than 1 in 100,000 individuals affected worldwide | ATRX | ATRX XH2 XNP Alpha Thalassemia/Mental Retardation Syndrome X-Linked | Alpha-thalassemia-X-linked intellectual disability (ATR-X) syndrome is a rare genetic disorder characterized by a combination of intellectual disability, distinctive facial features, and alpha-thalassemia, a blood disorder involving reduced production of hemoglobin. Individuals with ATR-X syndrome typically exhibit developmental delays, speech difficulties, and various physical abnormalities such as skeletal anomalies and genital abnormalities in males. This X-linked condition is caused by mutations in the ATRX gene, which plays a critical role in chromatin remodeling and gene expression regulation. The severity of symptoms can vary widely among affected individuals, and management primarily focuses on supportive care and addressing specific symptoms associated with the syndrome. | ATRX chromatin remodeler | ||
| 41 | Alternating hemiplegia of childhood | 1 in 1 million individuals | ATP1A2;CACNA1A;SLC1A3;ATP1A3 | ATP1A2 (ATPase Na+/K+ Transporting Subunit Alpha 2) Alias: FHM2, ATP1B, MHP2, NA+/K+ ATPase subunit alpha-2, Sodium/potassium-transporting ATPase alpha-2 chain CACNA1A (Calcium Voltage-Gated Channel Subunit Alpha1 A) Alias: CACNL1A4, CAV2.1, FHM, SCA6, CACNL1A4R, CACNL1A4S, CACNL1A4L, CACNL1A4B, CACNL1A4D, CACNL1A4F, CACNL1A4H, CACNL1A4T, CACNL1A4V, CACNL1A4X, CACNL1A4Y, CACNL1A4Z, Voltage-gated calcium channel subunit alpha Cav2.1 SLC1A3 (Solute Carrier Family 1 Member 3) Alias: EAAT1, GLAST, Excitatory amino acid transporter 1, Solute carrier family 1 member 3 ATP1A3 (ATPase Na+/K+ Transporting Subunit Alpha 3) Alias: ATPase alpha 3, ATP1B, ATP1A3L, ATPase Na+/K+ transporting subunit alpha-3 | Alternating hemiplegia of childhood (AHC) is a rare neurological disorder characterized by recurrent episodes of paralysis that typically affect one side of the body or the other, or both sides simultaneously. These episodes can occur spontaneously or be triggered by various factors such as physical activity, stress, or excitement. In addition to hemiplegia, individuals with AHC may experience other symptoms including dystonia, choreoathetosis, and cognitive impairment. The condition usually begins in infancy or early childhood and tends to persist throughout life, although the severity and frequency of episodes may vary. AHC is often caused by mutations in the ATP1A3 gene, which encodes a protein involved in the regulation of ion transport in nerve cells. Treatment options are limited and primarily focus on managing symptoms and improving quality of life for affected individuals. | ATPase Na+/K+ transporting subunit alpha 2;calcium voltage-gated channel subunit alpha1 A;solute carrier family 1 member 3;ATPase Na+/K+ transporting subunit alpha 3 | ||
| 42 | Alveolar rhabdomyosarcoma | 1 case per 1 million children and adolescents | TP53;FOXO1;PAX7;PAX3;NF1 | TP53 (Tumor Protein P53) Alias: p53, Cellular tumor antigen p53, Phosphoprotein p53, Tumor suppressor p53 FOXO1 (Forkhead Box O1) Alias: FKHR, Forkhead in rhabdomyosarcoma, Forkhead box protein O1, Forkhead box protein O1A, FOXO1A PAX7 (Paired Box 7) Alias: HUP1, PAX7c, PAX7e, PAX7f, PAX7h PAX3 (Paired Box 3) Alias: HUP2, WS1, Pax-3, WS, WS1S NF1 (Neurofibromin 1) Alias: Neurofibromin, Neurofibromatosis type I, NF-I, Von Recklinghausen disease, NFNS, VRNF | Alveolar rhabdomyosarcoma (ARMS) is a rare and aggressive type of cancer that primarily affects children and young adults. It arises from skeletal muscle cells and typically manifests as a rapidly growing tumor, most commonly found in the extremities, trunk, or genitourinary region. ARMS is characterized by its small round blue cell morphology under the microscope, with genetic abnormalities often involving the fusion of the PAX3 or PAX7 gene with the FOXO1 gene. Despite advancements in treatment, including chemotherapy, radiation therapy, and surgery, the prognosis for ARMS remains challenging, with a significant risk of metastasis and recurrence. Early detection and multidisciplinary management are essential for improving outcomes in patients with this aggressive malignancy. | tumor protein p53;forkhead box O1;paired box 7;paired box 3;neurofibromin 1 | ||
| 43 | Amelocerebrohypohidrotic syndrome | few dozen cases reported worldwide | SLC13A5;ROGDI | SLC13A5 (Solute Carrier Family 13 Member 5) Alias: NaCT (Sodium-coupled citrate transporter), INDY (I'm not dead yet), C6orf91 ROGDI (ROGD domain-containing protein I) Alias: KIAA1161 | Amelocerebrohypohidrotic syndrome (ACHS), also known as Kohlschütter-Tönz syndrome, is a rare genetic disorder characterized by a combination of dental abnormalities, neurological impairments, and reduced ability to sweat. Individuals with ACHS typically present with early-onset, severe developmental delay, intellectual disability, and epilepsy. Dental anomalies, such as thin enamel, small or absent teeth, and dental caries, are prominent features of the syndrome. Additionally, affected individuals may exhibit hypohidrosis or anhidrosis, leading to impaired thermoregulation and an increased risk of overheating. ACHS is inherited in an autosomal recessive manner and is caused by mutations in the FAM20A gene. Management of ACHS involves multidisciplinary care focusing on addressing developmental, neurological, and dental needs, along with strategies to manage heat intolerance. | solute carrier family 13 member 5;rogdi atypical leucine zipper | N2A (Neuro-2a) - Mouse neuroblastoma cells. PC12 - Rat pheochromocytoma cells. NIH 3T3 - Mouse fibroblast cells. | |
| 44 | Amyotrophic lateral sclerosis | 4 to 6 cases per 100,000 people in most populations | TREM2;UNC13A;CHMP2B;GLT8D1;DAO;DCTN1;EPHA4;ERBB4;FUS;GLE1;ANG;HNRNPA1;ANXA11;MATR3;NEFH;NEK1;PFN1;PON1;PON2;PON3;PPARGC1A;PRPH;ATXN2;SOD1;SQSTM1;TAF15;TARDBP;TBK1;UBQLN2;CFAP410;VAPB;VCP;CHCHD10;CCNF;FIG4;OPTN | TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) Alias: TREM-2, Trem2a UNC13A (Unc-13 Homolog A) Alias: Munc13-1 CHMP2B (Charged Multivesicular Body Protein 2B) Alias: Chromatin Modifying Protein 2B, Vacuolar Protein Sorting 2B GLT8D1 (Glycosyltransferase 8 Domain Containing 1) Alias: GLT8D1 DAO (D-Amino Acid Oxidase) Alias: D-amino-acid oxidase DCTN1 (Dynactin Subunit 1) Alias: Dynactin 1 EPHA4 (EPH Receptor A4) Alias: EPH-A4 ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) Alias: Her4, Tyrosine kinase-type cell surface receptor HER4, Proto-oncogene c-ErbB-4 FUS (Fused in Sarcoma) Alias: TLS, hnRNP P2, Translocated in Liposarcoma GLE1 (GLE1 RNA Export Mediator) Alias: GLE1L ANG (Angiogenin) Alias: Angiogenin, Ribonuclease 5 HNRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) Alias: hnRNP A1, Ribonucleoprotein A1 ANXA11 (Annexin A11) Alias: Annexin XI, Annexin-11 MATR3 (Matrin 3) Alias: Matrin-3, Neuroblastoma-specific antigen NB NEFH (Neurofilament Heavy) Alias: NFH, NEF3, Neurofilament triplet H protein NEK1 (NIMA Related Kinase 1) Alias: NIMA-related kinase 1, NimA-related protein kinase 1 PFN1 (Profilin 1) Alias: Profilin-1 PON1 (Paraoxonase 1) Alias: Serum paraoxonase/arylesterase 1, Aromatic esterase 1 PON2 (Paraoxonase 2) Alias: Serum paraoxonase/arylesterase 2, Aromatic esterase 2 PON3 (Paraoxonase 3) Alias: Serum paraoxonase/arylesterase 3, Aromatic esterase 3 PPARGC1A (PPARG Coactivator 1 Alpha) Alias: PGC-1alpha, PPAR-gamma coactivator 1-alpha PRPH (Peripherin) Alias: Peripherin ATXN2 (Ataxin 2) Alias: Spinocerebellar ataxia type 2 protein, Spinocerebellar ataxia type 2 protein SOD1 (Superoxide Dismutase 1) Alias: Cu-Zn superoxide dismutase, Superoxide dismutase [Cu-Zn] SQSTM1 (Sequestosome 1) Alias: p62, Ubiquitin-binding protein p62 TAF15 (TATA-Box Binding Protein Associated Factor 2N) Alias: TAF2N, RBP56 TARDBP (TAR DNA Binding Protein) Alias: TDP-43, TAR DNA-binding protein 43 TBK1 (TANK Binding Kinase 1) Alias: NF-kappa-B-activating kinase, T2K UBQLN2 (Ubiquilin 2) Alias: UBQLN2, Ubiquitin-like protein 2 CFAP410 (Cilia And Flagella Associated Protein 410) Alias: CFAP410 VAPB (VAMP Associated Protein B And C) Alias: VAP-B, VAP-B/C VCP (Valosin Containing Protein) Alias: p97, Transitional endoplasmic reticulum ATPase CHCHD10 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10) Alias: MICOS complex subunit Mic25, Coiled-coil-helix-coiled-coil-helix domain-containing protein 10 CCNF (Cyclin F) Alias: FBXO1, Cyclin-F FIG4 (FIG4 Phosphoinositide 5-Phosphatase) Alias: Sac3, Sac domain-containing protein 3 OPTN (Optineurin) Alias: GLC1E, FIP2 | Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder characterized by the gradual degeneration and loss of motor neurons in the brain and spinal cord. This leads to muscle weakness, paralysis, and ultimately, respiratory failure, typically within 2 to 5 years of symptom onset. While the exact cause of ALS remains unclear, it is believed to involve a combination of genetic and environmental factors. There is currently no cure for ALS, and treatment primarily focuses on managing symptoms and improving quality of life through medication, therapy, and supportive care. | triggering receptor expressed on myeloid cells 2;unc-13 homolog A;charged multivesicular body protein 2B;glycosyltransferase 8 domain containing 1;D-amino acid oxidase;dynactin subunit 1;EPH receptor A4;erb-b2 receptor tyrosine kinase 4;FUS RNA binding protein;GLE1 RNA export mediator;angiogenin;heterogeneous nuclear ribonucleoprotein A1;annexin A11;matrin 3;neurofilament heavy chain;NIMA related kinase 1;profilin 1;paraoxonase 1;paraoxonase 2;paraoxonase 3;PPARG coactivator 1 alpha;peripherin;ataxin 2;superoxide dismutase 1;sequestosome 1;TATA-box binding protein associated factor 15;TAR DNA binding protein;TANK binding kinase 1;ubiquilin 2;cilia and flagella associated protein 410;VAMP associated protein B and C;valosin containing protein;coiled-coil-helix-coiled-coil-helix domain containing 10;cyclin F;FIG4 phosphoinositide 5-phosphatase;optineurin | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. HEK293 - Human embryonic kidney cells. COS-7 - Monkey kidney fibroblast cells. | |
| 45 | Anaplastic oligodendroglioma | approximately 2-5% of all gliomas, which are tumors that arise from glial cells in the brain. Anaplastic oligodendrogliomas are more commonly diagnosed in adults, typically between the ages of 30 and 50 years old | IDH2;POT1 | IDH2 (Isocitrate Dehydrogenase [NADP(+)] 2, Mitochondrial) Alias: IDP, IDP-2, IDH, IDHM, IDP-2, ICD-M, IDP-B, IDH2A, mNADP-IDH, R155H, R172G, R172S, R172K, R172M POT1 (Protection of Telomeres 1) Alias: TINF2, TP2, TPP1, POT1-TPP1, TINT1, PT1, THW, POT1-TPP1 alpha-beta complex, hPot1 | Anaplastic oligodendroglioma is a type of malignant brain tumor that arises from oligodendrocytes, the cells responsible for producing the myelin sheath around nerve fibers in the brain. It is characterized by aggressive growth and infiltration into surrounding brain tissue. Anaplastic oligodendrogliomas are typically high-grade tumors, exhibiting cellular atypia and increased mitotic activity. They often present with symptoms such as seizures, headaches, and neurological deficits, depending on their location within the brain. Treatment typically involves a combination of surgical resection, radiation therapy, and chemotherapy, with prognosis varying depending on factors such as tumor grade, extent of surgical resection, and molecular characteristics. | isocitrate dehydrogenase (NADP(+)) 2;protection of telomeres 1 | HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | |
| 46 | Aneurysm-osteoarthritis syndrome | less than 1 in 100,000 individuals | SMAD3 | less than 1 in 100,000 individuals | Aneurysm-osteoarthritis syndrome (AOS) is a rare genetic disorder characterized by the presence of arterial aneurysms and early-onset osteoarthritis. It is primarily caused by mutations in the SMAD3 gene, leading to abnormalities in the connective tissue. Individuals with AOS often present with arterial dilations, particularly affecting the aorta and other major arteries, which can predispose them to potentially life-threatening complications such as dissection or rupture. Additionally, patients commonly experience symptoms of osteoarthritis at a young age, affecting multiple joints and leading to pain and mobility issues. Early diagnosis and management are crucial to mitigate the risk of cardiovascular events and to address the musculoskeletal manifestations of the syndrome. | SMAD family member 3 | ||
| 47 | Aortic aneurysm, familial thoracic 4 | 1 in 5,000 to 10,000 individuals | MYH11 | SMHC (Smooth Muscle Myosin Heavy Chain) SMMHC (Smooth Muscle Myosin Heavy Chain) SMHH (Smooth Muscle Heavy Chain Myosin) MYHBC (Myosin Heavy Chain, Smooth Muscle, B isoform) SMC-2 (Smooth Muscle Myosin Heavy Chain 2) | Familial thoracic aortic aneurysm and dissection (FTAAD) type 4 is a genetic disorder characterized by the weakening of the aortic wall, leading to the formation of an aneurysm. Specifically, FTAAD4 is associated with mutations in the MYH11 gene, which encodes a protein important for the structure and function of smooth muscle cells in the aortic wall. This condition predisposes individuals to the development of thoracic aortic aneurysms, which can lead to life-threatening complications such as aortic dissection or rupture. FTAAD4 typically exhibits an autosomal dominant pattern of inheritance, meaning that individuals with a single copy of the mutated gene have an increased risk of developing the condition. Early detection through genetic testing and regular monitoring of aortic health are essential for managing FTAAD4 and reducing the risk of potentially catastrophic complications. | myosin heavy chain 11 | ||
| 48 | Aplasia cutis congenita | 1 in 10,000 births | PLEC;DLL4;ITGB4;BMS1 | PLEC (Plectin) Alias: HD1, BPAG1, Hemidesmosomal protein 1, Epidermolysis bullosa simplex with pyloric atresia protein DLL4 (Delta-like 4) Alias: Delta4, Delta-like ligand 4, Delta-like protein 4 ITGB4 (Integrin Subunit Beta 4) Alias: CD104, ITGB4B, Integrin beta-4 BMS1 (BMS1 Ribosome Biogenesis Factor) Alias: HSPC117, rRNA processing protein BMS1 homolog | Aplasia cutis congenita (ACC) is a rare congenital disorder characterized by the absence of skin, typically at birth. It can occur anywhere on the body but most commonly affects the scalp. ACC lesions can vary in size and depth, ranging from small, shallow areas of missing skin to larger defects involving underlying tissue, such as the skull. The exact cause is often unknown, though it can be associated with genetic factors, vascular abnormalities, or teratogenic exposures during pregnancy. Treatment depends on the severity and location of the lesions and may involve conservative management, surgical repair, or skin grafting. | plectin;delta like canonical Notch ligand 4;integrin subunit beta 4;BMS1 ribosome biogenesis factor | ||
| 49 | Aromatic L-amino acid decarboxylase deficiency | fewer than 1 in 1 million individuals worldwide | DDC | AADC (Aromatic L-Amino Acid Decarboxylase) DDC (Dopa Decarboxylase) DDC DOPA Decarboxylase Aromatic-L-amino-acid decarboxylase | Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder impairing neurotransmitter production in the brain. Symptoms, appearing in infancy, include developmental delay, movement disorders, and autonomic dysfunction. Diagnosis involves genetic testing and neurotransmitter metabolite analysis. Treatment focuses on symptom management with dopamine agonists and serotonin precursors, while gene therapy is being explored. | dopa decarboxylase | ||
| 50 | Arterial tortuosity syndrome | less than 1 in 1 million individuals | SLC2A10 | GLUT10 GLU10 Facilitative glucose transporter member 10 ATG | Arterial Tortuosity Syndrome (ATS) is a rare genetic disorder characterized by the abnormal twisting and lengthening (tortuosity) of the arteries throughout the body. This can lead to various cardiovascular complications, such as aneurysms, stenosis, and increased risk of arterial rupture. ATS is caused by mutations in the SLC2A10 gene, which is inherited in an autosomal recessive pattern. Common symptoms include elongated facial features, hyperextensible skin, joint hypermobility, and respiratory issues due to vascular abnormalities. Early diagnosis and regular monitoring are crucial for managing cardiovascular risks associated with ATS. | solute carrier family 2 member 10 | ||
| 51 | Aspartylglucosaminuria | approximately 1 in 1,000,000 globally | AGA | Aspartylglucosaminase AGA1 Aspartylglucosaminidase precursor | Aspartylglucosaminuria (AGU) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the AGA gene, leading to a deficiency of the enzyme aspartylglucosaminidase. This enzyme deficiency results in the accumulation of glycoasparagines in tissues, causing progressive developmental delay, intellectual disability, coarse facial features, skeletal abnormalities, and a decline in motor and speech skills. Behavioral issues and psychiatric symptoms may also occur. Diagnosis is confirmed through genetic testing and enzyme assays, and while there is no cure, supportive treatments can help manage the symptoms. | aspartylglucosaminidase | ||
| 52 | Ataxia-hypogonadism-choroidal dystrophy syndrome | less than 1 in 1,000,000 individuals | PNPLA6 | Neuropathy Target Esterase (NTE) NEU NTE-related esterase Phospholipase B-like 3 Patatin-like phospholipase domain-containing protein 6 | Ataxia-hypogonadism-choroidal dystrophy syndrome, also known as Woods syndrome, is a rare genetic disorder characterized by a triad of symptoms: progressive ataxia leading to coordination and balance issues, hypogonadism resulting in underdeveloped reproductive organs and impaired fertility, and choroidal dystrophy causing vision impairment. This syndrome follows an autosomal recessive pattern of inheritance and is caused by mutations in the PNPLA6 gene, which encodes an enzyme involved in lipid metabolism and other cellular processes. Due to its rarity and complex symptomatology, diagnosis and management often require a multidisciplinary approach involving neurologists, endocrinologists, ophthalmologists, and genetic counselors. | patatin like phospholipase domain containing 6 | ||
| 53 | Atrial septal defect, ostium primum type | 1 in 1,500 live births | TLL1 | TLL dJ840G16.1 tolloid-like protein 1 TM27 | An atrial septal defect (ASD), ostium primum type, is a congenital heart defect characterized by an opening in the lower part of the atrial septum, near the atrioventricular valves. This type of ASD is associated with defects in the endocardial cushion and often occurs in conjunction with other abnormalities, such as cleft mitral valves or ventricular septal defects. Symptoms can range from none to significant, including breathlessness, fatigue, and palpitations, depending on the size of the defect and associated complications. Treatment typically involves surgical correction to close the defect and repair any associated anomalies. | tolloid like 1 | ||
| 54 | Atypical Rett syndrome | 1 in 10,000 to 1 in 15,000 live births | MECP2;CDKL5;GABBR2;NTNG1;SMC1A | MECP2 (Methyl-CpG Binding Protein 2) Alias: RTT, RS, MRX16, MRX79, PPMX, Rett Syndrome CDKL5 (Cyclin Dependent Kinase Like 5) Alias: STK9, Serine/Threonine Kinase 9, Epileptic Encephalopathy, Early Infantile, 2 GABBR2 (Gamma-Aminobutyric Acid Type B Receptor Subunit 2) Alias: GPR51, GABABR2 NTNG1 (Netrin G1) Alias: Netrin-G1, LRRC4C SMC1A (Structural Maintenance of Chromosomes 1A) Alias: SMC1, SMC1L1 | Atypical Rett syndrome is a neurodevelopmental disorder that shares some characteristics with classic Rett syndrome but varies in its clinical presentation. Unlike classic Rett syndrome, which primarily affects females and is caused by mutations in the MECP2 gene, atypical Rett syndrome may have different genetic causes, such as mutations in the CDKL5 or FOXG1 genes. Symptoms include developmental delays, intellectual disability, motor abnormalities, and sometimes seizures. The onset and severity of symptoms can be highly variable, leading to its classification into various subtypes. Diagnosis is based on clinical criteria and genetic testing. | methyl-CpG binding protein 2;cyclin dependent kinase like 5;gamma-aminobutyric acid type B receptor subunit 2;netrin G1;structural maintenance of chromosomes 1A | ||
| 55 | Auriculocondylar syndrome | fewer than 1 in 1,000,000 individuals | EDN1;GNAI3;PLCB4 | EDN1 (Endothelin 1) Alias: ET-1, PPET1, Preproendothelin-1 GNAI3 (G Protein Subunit Alpha I3) Alias: Gi3 alpha, Gi3A, GNAI3A, GNAI3B PLCB4 (Phospholipase C Beta 4) Alias: PLCB-ETA, Phosphoinositide phospholipase C-beta-4, PI-PLC | Auriculocondylar syndrome (ACS) is a rare genetic disorder characterized by facial and mandibular abnormalities such as micrognathia (small jaw), auricular anomalies (malformed external ears), facial asymmetry, and temporomandibular joint (TMJ) issues. It is typically inherited in an autosomal dominant pattern and linked to mutations in the PLCB4, GNAI3, or EDN1 genes. Management of ACS involves a multidisciplinary approach to address the specific symptoms and structural abnormalities present in affected individuals. | endothelin 1;G protein subunit alpha i3;phospholipase C beta 4 | ||
| 56 | Autosomal agammaglobulinemia | less than 1 in 1,000,000 individuals worldwide | PIK3R1;IGHM;TCF3;LRRC8A;IGLL1;CD79B;CD79A;BLNK | PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) Aliases: GRB1, p85-ALPHA, p85, p50-ALPHA, p55-ALPHA, p85α IGHM (Immunoglobulin Heavy Constant Mu) Aliases: IgM, IGM TCF3 (Transcription Factor 3) Aliases: E2A, ITF1, bHLHb21, VDIR LRRC8A (Leucine Rich Repeat Containing 8 VRAC Subunit A) Aliases: SWELL1, FRTL, LRR8A IGLL1 (Immunoglobulin Lambda Like Polypeptide 1) Aliases: 14.1, AGM1, IGO, VPREB2 CD79B (CD79b Molecule) Aliases: B29, IGB, AGM6 CD79A (CD79a Molecule) Aliases: MB-1, IGA, MB1 BLNK (B Cell Linker) Aliases: SLP65, BASH, BCA, BLS, SLP-65 | Autosomal agammaglobulinemia is a rare primary immunodeficiency disorder characterized by a marked reduction or absence of immunoglobulins (antibodies) in the blood. Unlike the more common X-linked agammaglobulinemia, this form is inherited in an autosomal recessive manner, meaning both copies of a gene must be mutated for the disease to manifest. Individuals with this condition have a severe reduction in B cells, which are crucial for producing antibodies. As a result, they are highly susceptible to recurrent bacterial infections starting in infancy or early childhood. Treatment often involves regular immunoglobulin replacement therapy to boost the immune system and prevent infections. | phosphoinositide-3-kinase regulatory subunit 1;immunoglobulin heavy constant mu;transcription factor 3;leucine rich repeat containing 8 VRAC subunit A;immunoglobulin lambda like polypeptide 1;CD79b molecule;CD79a molecule;B cell linker | PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | |
| 57 | Autosomal dominant Alport syndrome | approximately 1 in 50,000 live births | COL4A3;COL4A4 | COL4A3 (Collagen Type IV Alpha 3 Chain) Alias: Arresten, Goodpasture Antigen, GP, GPBP, MGC92627 Database IDs: HGNC ID: 2204 NCBI Gene ID: 1285 Ensembl: ENSG00000169031 OMIM: 120070 COL4A4 (Collagen Type IV Alpha 4 Chain) Alias: Alport Syndrome, Autosomal Recessive, Alport Syndrome, Autosomal Dominant, AS, ATS, MGC125929 Database IDs: HGNC ID: 2206 NCBI Gene ID: 1286 Ensembl: ENSG00000197587 OMIM: 120131 | Autosomal dominant Alport syndrome (ADAS) is a genetic disorder characterized by progressive kidney disease, hearing loss, and eye abnormalities. It results from mutations in the COL4A3 or COL4A4 genes, which encode type IV collagen, a crucial component of the basement membranes in the kidneys, inner ear, and eyes. Unlike the more common X-linked Alport syndrome, ADAS affects both males and females similarly, though the severity can vary. Patients often experience hematuria (blood in urine) from a young age, with proteinuria and kidney function decline developing later in life. Early diagnosis and management are essential to mitigate progression to end-stage renal disease. | collagen type IV alpha 3 chain;collagen type IV alpha 4 chain | ||
| 58 | Autosomal dominant centronuclear myopathy | less than 1 in 1,000,000 individuals | RYR1;BIN1;MTMR14;MYF6;DNM2 | RYR1 (Ryanodine Receptor 1) Alias: RYR, MHS, MHS1, CCO, RYR-1 BIN1 (Bridging Integrator 1) Alias: AMPH2, ALP, SH3P9, MGC111040, MYC box-dependent-interacting protein 1 MTMR14 (Myotubularin Related Protein 14) Alias: Jumpy, KIAA0833, MTMRL MYF6 (Myogenic Factor 6) Alias: MRF4, HERF1, MYF-6, bHLHc4 DNM2 (Dynamin 2) Alias: CMT2M, CMTDI1, DYN2, LCCS5, DYNII | Autosomal dominant centronuclear myopathy (ADCNM) is a rare genetic disorder characterized by muscle weakness and wasting, particularly affecting the muscles closest to the center of the body, such as those in the neck, shoulders, and hips. This condition is caused by mutations in the DNM2 gene, which encodes dynamin-2, a protein involved in muscle cell structure and function. Symptoms typically appear in adolescence or early adulthood and can include difficulty walking, lifting, and other activities requiring muscle strength. The severity of the condition can vary, with some individuals experiencing mild symptoms and others having more significant muscle impairment | ryanodine receptor 1;bridging integrator 1;myotubularin related protein 14;myogenic factor 6;dynamin 2 | ||
| 59 | Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons | approximately 1 in 25,000 to 1 in 40,000 individuals worldwide | DCAF8 | WDR42B (WD Repeat Domain 42B) DDB1 and CUL4 Associated Factor 8 WD Repeat-Containing Protein 42B | Autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2) with giant axons is a subtype of Charcot-Marie-Tooth (CMT) disease, a group of inherited peripheral neuropathies. In this specific subtype, individuals inherit a mutated gene from one parent, leading to the development of peripheral nerve damage. CMT2 with giant axons is characterized by the presence of abnormally enlarged axons in nerve biopsies, which can contribute to the clinical manifestations of the disease. Symptoms typically include muscle weakness and atrophy, sensory loss, and decreased reflexes, primarily affecting the feet and legs initially and progressing upwards over time. Genetic testing can confirm the diagnosis, with mutations in genes such as MFN2 and GDAP1 commonly associated with this subtype. Management often involves symptomatic treatment and physical therapy to improve muscle strength and function, as well as genetic counseling for affected individuals and their families. | DDB1 and CUL4 associated factor 8 | ||
| 60 | Autosomal dominant dopa-responsive dystonia | approximately 1 in 1 million individuals | IMPDH2;GCH1 | IMPDH2 (Inosine-5'-Monophosphate Dehydrogenase 2) Alias: IMPD2, IMD2 GCH1 (GTP Cyclohydrolase 1) Alias: DYT5, GCH, GTP-CH-I | Autosomal dominant dopa-responsive dystonia (DYT5a) is a rare genetic movement disorder characterized by involuntary muscle contractions, tremors, and abnormal postures. It typically begins in childhood or adolescence and is caused by mutations in the GCH1 gene, affecting dopamine production in the brain. Symptoms often respond well to low doses of levodopa, a precursor to dopamine, leading to significant improvement in motor function. Genetic testing is necessary for diagnosis, and treatment involves long-term management with levodopa therapy. Early detection and appropriate treatment can significantly improve quality of life for affected individuals. | inosine monophosphate dehydrogenase 2;GTP cyclohydrolase 1 | HEK293-Human embryonic kidney cells, HepG2-Human liver cancer cells Rat fibroblast cell lines (like L6), Rat liver cells SK-N-SH -Human neuroblastoma cells (SK-N-SH) hCMEC/D3 - Human brain endothelial cells PC12- Rat pheochromocytoma cells Rat brain microvascular endothelial cell | |
| 61 | Autosomal dominant focal dystonia, DYT25 type | only a few reported cases worldwide | GNAL | Gαolf G alpha-olf | Autosomal dominant focal dystonia, specifically DYT25 type, is a rare genetic disorder characterized by involuntary muscle contractions leading to abnormal movements and postures, typically localized to specific body regions like the neck or hand. Caused by mutations in the GNAL gene, which disrupts normal basal ganglia function, symptoms usually emerge in adulthood and vary in severity. Treatment options include medications, botulinum toxin injections, or deep brain stimulation surgery, aiming to alleviate symptoms and improve quality of life for affected individuals. | G protein subunit alpha L | SH-SY5Y-Human neuroblastoma cells HEK293-Human embryonic kidney 293 (HEK293) cells Rat pheochromocytoma cells (PC12) Rat brain-derived cell lines, such as C6 glioma cells | |
| 62 | Autosomal dominant generalized dystrophic epidermolysis bullosa | 1 in 50,000 to 1 in 100,000 live births | COL7A1 | Epidermolysis Bullosa Dystrophica EBD1 Collagen, Type VII, Alpha-1 | Autosomal dominant generalized dystrophic epidermolysis bullosa (AD-GDEB) is a rare genetic disorder characterized by fragile skin that easily blisters and tears in response to minor trauma. This condition is caused by mutations in the COL7A1 gene, which encodes type VII collagen, a crucial component of anchoring fibrils that secure the epidermis to the underlying dermis. Individuals with AD-GDEB typically present with widespread blistering at birth or early infancy, which can lead to scarring, milia (tiny white bumps), and nail dystrophy. Despite being a lifelong condition, the severity can vary widely among affected individuals. | collagen type VII alpha 1 chain | Human dermal fibroblasts Human keratinocytes Rat skin fibroblast cell lines (e.g., L929 cells) Rat epithelial cell lines (e.g., Rat2 cells) | |
| 63 | Autosomal dominant generalized epidermolysis bullosa simplex, intermediate form | approximately 7 to 8 per million live births | KRT5;KRT14 | KRT5 (Keratin 5) Aliases: CK5 (Cytokeratin 5) K5 Keratin, type II cytoskeletal 5 Cytokeratin-5 KRT14 (Keratin 14) Aliases: CK14 (Cytokeratin 14) K14 Keratin, type I cytoskeletal 14 Cytokeratin-14 | Autosomal dominant generalized epidermolysis bullosa simplex, intermediate form, is a rare genetic disorder characterized by skin fragility leading to blistering and erosions, often triggered by minor trauma. The condition is caused by mutations in the KRT5 or KRT14 genes, which encode keratin proteins essential for skin integrity. Blistering typically appears at birth or in early infancy and may affect widespread areas of the body. While the condition is lifelong, its severity can vary, with some individuals experiencing milder symptoms over time. There is no cure, but management focuses on wound care, preventing infections, and minimizing trauma to the skin. | keratin 5;keratin 14 | MCF-7 - Human breast cancer cells. HEK293 - Human embryonic kidney cells. Kera - Human keratinocytes. | |
| 64 | dominant generalized epidermolysis bullosa simplex, severe form | approximately 6-30 cases per 1 million live births | KRT5;KRT14 | KRT5 (Keratin 5) Aliases: CK5 (Cytokeratin 5) K5 Keratin, type II cytoskeletal 5 Cytokeratin-5 KRT14 (Keratin 14) Aliases: CK14 (Cytokeratin 14) K14 Keratin, type I cytoskeletal 14 Cytokeratin-14 | Autosomal dominant generalized epidermolysis bullosa simplex (AD-GEBS), severe form, is a genetic skin disorder characterized by fragile skin that blisters easily in response to minor trauma. It is caused by mutations in the KRT5 or KRT14 genes, which encode keratin proteins essential for skin integrity. Symptoms typically present at birth or in early infancy and include widespread blistering, erosions, and sometimes nail dystrophy. The severe form can lead to significant complications, including infections and impaired quality of life. The condition is inherited in an autosomal dominant pattern, meaning only one copy of the mutated gene is sufficient to cause the disorder. Treatment focuses on wound care, infection prevention, and pain management. | keratin 5;keratin 14 | HaCaT-Human keratinocytes Human epidermal stem cells RHEK1 Rat keratinocyte cell lines Rat skin fibroblast | |
| 65 | Autosomal dominant hypohidrotic ectodermal dysplasia | approximately 1 in 100,000 live births | EDARADD;KDF1;EDAR;TRAF6 | " EDARADD (EDAR-Associated Death Domain) Alias: EDAR-associated death domain protein, EDARADD KDF1 (Keratinocyte Differentiation Factor 1) Alias: KDF1, Keratinocyte Differentiation Factor 1 EDAR (Ectodysplasin A Receptor) Alias: Ectodysplasin A receptor, EDAR TRAF6 (TNF Receptor Associated Factor 6) Alias: TNF receptor-associated factor 6, TRAF6" | Autosomal dominant hypohidrotic ectodermal dysplasia (AD-HED) is a genetic disorder characterized by abnormalities in structures derived from the ectoderm, such as hair, teeth, nails, and sweat glands. It's caused by mutations in the EDA gene, affecting its protein product, which plays a crucial role in the development of these ectodermal structures. Individuals with AD-HED typically present with sparse hair, missing or malformed teeth, reduced ability to sweat, and abnormal nails. The severity of symptoms can vary widely among affected individuals, even within the same family. Treatment focuses on managing symptoms and may include dental prosthetics, artificial sweat supplementation, and supportive care for associated health issues. | EDAR associated death domain;keratinocyte differentiation factor 1;ectodysplasin A receptor;TNF receptor associated factor 6 | HaCaT-Human keratinocytes Human dermal fibroblasts HEK293-Human epithelial cells L929-Rat skin fibroblasts Rat keratinocyte cell lines THP-1 -Human monocytic cells MG-63 -Human osteoblastic cells ROS 17/2.8-Rat osteoblast cell lines L6-Rat fibroblast cell lines | |
| 66 | Autosomal dominant nocturnal frontal lobe epilepsy | 1 to 7 per 100,000 individuals | CHRNA2;CHRNA4;CHRNB2;CRH;CABP4;DEPDC5;KCNT1 | CHRNA2 (Cholinergic Receptor Nicotinic Alpha 2 Subunit) Alias: nAChRα2 CHRNA4 (Cholinergic Receptor Nicotinic Alpha 4 Subunit) Alias: nAChRα4 CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) Alias: nAChRβ2 CRH (Corticotropin Releasing Hormone) Alias: CRF, CRH-RF, CRH1 CABP4 (Calcium Binding Protein 4) Alias: CaBP4 DEPDC5 (DEP Domain Containing 5) Alias: KIAA1712 KCNT1 (Potassium Sodium-Activated Channel Subfamily T Member 1) Alias: SLACK, KCNT1, KNa1.1 | Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) is a rare form of epilepsy characterized by seizures that predominantly occur during sleep. It is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene from one parent is sufficient to cause the disorder. ADNFLE typically manifests with sudden, brief, and often violent seizures, including motor movements, vocalizations, and sometimes complex behaviors. These seizures can be difficult to control with medication and may require specialized treatment approaches. Mutations in genes encoding neuronal nicotinic acetylcholine receptors, such as CHRNA4 and CHRNB2, have been associated with ADNFLE. Early recognition and proper management are crucial for individuals with this condition to achieve optimal outcomes. | cholinergic receptor nicotinic alpha 2 subunit;cholinergic receptor nicotinic alpha 4 subunit;cholinergic receptor nicotinic beta 2 subunit;corticotropin releasing hormone;calcium binding protein 4;DEP domain containing 5, GATOR1 subcomplex subunit;potassium sodium-activated channel subfamily T member 1 | Human neuroblastoma cells (e.g., SH-SY5Y cells) Human embryonic kidney 293 (HEK293) cells (often used for expression studies) Rat cell lines: Rat pheochromocytoma cells (PC12 cells) Rat brain-derived cell lines (e.g., C6 glioma cells) | |
| 67 | Autosomal dominant non-syndromic intellectual disability | 1% of the global population is approximately 80 million people. 3% of the global population is approximately 240 million people. | PPP3CA;RAB11A;CAMK2A;CAMK2B;DEAF1;MED12L;ZMYND11;CDH15;TRPM3;KDM5B;ASH1L;CSNK2B;CUX1;KIRREL3;CLTC;MBD5;PRICKLE2;CHAMP1;DOCK8;DLL1;SET;BRSK2;SYNGAP1;TCF4;CACNA1I;CACNG2;CIC;SETD1B;TAOK1;DYNC1H1;EEF1A2;EPB41L1;ERBB4;GRIN1;GRIN2B;HIVEP2;ITSN1;KCNQ2;KCNQ5;MYT1L;NBEA;KIF1A | PPP3CA (Protein Phosphatase 3 Catalytic Subunit Alpha) Alias: CALNA, CALNA1, PP2BA RAB11A (RAB11A, Member RAS Oncogene Family) Alias: YL8, RAB11, RAB11A CAMK2A (Calcium/Calmodulin Dependent Protein Kinase II Alpha) Alias: CAMKA, CaMKII alpha CAMK2B (Calcium/Calmodulin Dependent Protein Kinase II Beta) Alias: CAMKB, CaMKII beta DEAF1 (Deformed Epidermal Autoregulatory Factor 1 Homolog) Alias: NUDR, SPN, DEAF-1 MED12L (Mediator Complex Subunit 12 Like) No common aliases ZMYND11 (Zinc Finger MYND-Type Containing 11) Alias: BS69, ZNF822 CDH15 (Cadherin 15) Alias: M-Cadherin, CDH14 TRPM3 (Transient Receptor Potential Cation Channel Subfamily M Member 3) Alias: LTRPC3 KDM5B (Lysine Demethylase 5B) Alias: JARID1B, PLU1, RBP2-H1 ASH1L (ASH1 Like Histone Lysine Methyltransferase) Alias: KMT2H CSNK2B (Casein Kinase 2 Beta) Alias: CK2B, G5A, CSK2B CUX1 (Cut Like Homeobox 1) Alias: CDP, CUTL1 KIRREL3 (Kin of IRRE Like 3) Alias: KIRREL2, NEPH2 CLTC (Clathrin Heavy Chain) Alias: CHC, CLH-22 MBD5 (Methyl-CpG Binding Domain Protein 5) Alias: RSTS1 PRICKLE2 (Prickle Planar Cell Polarity Protein 2) Alias: EPM5, RICKLE2 CHAMP1 (Chromosome Alignment Maintaining Phosphoprotein 1) No common aliases DOCK8 (Dedicator of Cytokinesis 8) Alias: ZIR8 DLL1 (Delta Like Canonical Notch Ligand 1) Alias: DELTA1, H-Delta-1 SET (SET Nuclear Proto-Oncogene) Alias: PHAPII, IGAAD BRSK2 (BR Serine/Threonine Kinase 2) Alias: SAD1B SYNGAP1 (Synaptic Ras GTPase Activating Protein 1) Alias: MRD5 TCF4 (Transcription Factor 4) Alias: E2-2, ITF2, SEF2-1 CACNA1I (Calcium Voltage-Gated Channel Subunit Alpha1 I) Alias: Cav3.3 CACNG2 (Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 2) Alias: STARGAZIN CIC (Capicua Transcriptional Repressor) Alias: HMGIYC SETD1B (SET Domain Containing 1B) Alias: KMT2G TAOK1 (TAO Kinase 1) Alias: KIAA1361, PSK1 DYNC1H1 (Dynein Cytoplasmic 1 Heavy Chain 1) Alias: DHC1, DHC1A EEF1A2 (Eukaryotic Translation Elongation Factor 1 Alpha 2) Alias: EEF1AL EPB41L1 (Erythrocyte Membrane Protein Band 4.1 Like 1) Alias: 4.1N, NF2L1 ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) Alias: HER4 GRIN1 (Glutamate Ionotropic Receptor NMDA Type Subunit 1) Alias: NMD-R1, NR1, NMDAR1 GRIN2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2B) Alias: NR2B, NMDAR2B HIVEP2 (Human Immunodeficiency Virus Type I Enhancer Binding Protein 2) Alias: MIBP1, PRDII-BF1 ITSN1 (Intersectin 1) Alias: SH3D1A, ITSN KCNQ2 (Potassium Voltage-Gated Channel Subfamily Q Member 2) Alias: KV7.2, BFNC, ENB1 KCNQ5 (Potassium Voltage-Gated Channel Subfamily Q Member 5) Alias: KV7.5 MYT1L (Myelin Transcription Factor 1 Like) No common aliases NBEA (Neurobeachin) Alias: A830005K05Rik KIF1A (Kinesin Family Member 1A) Alias: KIAA4012 | Autosomal dominant non-syndromic intellectual disability (ADNSID) is a type of intellectual disability inherited in an autosomal dominant pattern, meaning only one copy of the mutated gene from either parent is sufficient to cause the condition. Unlike syndromic intellectual disabilities, ADNSID is characterized by cognitive impairment without additional physical, neurological, or metabolic abnormalities. The severity of the intellectual disability can vary widely among affected individuals. Genetic mutations in various genes, such as SYNGAP1, ARID1B, and CHD2, have been associated with ADNSID. Diagnosis typically involves genetic testing, and management focuses on supportive therapies tailored to the individual's needs. | protein phosphatase 3 catalytic subunit alpha;RAB11A, member RAS oncogene family;calcium/calmodulin dependent protein kinase II alpha;calcium/calmodulin dependent protein kinase II beta;DEAF1 transcription factor;mediator complex subunit 12L;zinc finger MYND-type containing 11;cadherin 15;transient receptor potential cation channel subfamily M member 3;lysine demethylase 5B;ASH1 like histone lysine methyltransferase;casein kinase 2 beta;cut like homeobox 1;kirre like nephrin family adhesion molecule 3;clathrin heavy chain;methyl-CpG binding domain protein 5;prickle planar cell polarity protein 2;chromosome alignment maintaining phosphoprotein 1;dedicator of cytokinesis 8;delta like canonical Notch ligand 1;SET nuclear proto-oncogene;BR serine/threonine kinase 2;synaptic Ras GTPase activating protein 1;transcription factor 4;calcium voltage-gated channel subunit alpha1 I;calcium voltage-gated channel auxiliary subunit gamma 2;capicua transcriptional repressor;SET domain containing 1B, histone lysine methyltransferase;TAO kinase 1;dynein cytoplasmic 1 heavy chain 1;eukaryotic translation elongation factor 1 alpha 2;erythrocyte membrane protein band 4.1 like 1;erb-b2 receptor tyrosine kinase 4;glutamate ionotropic receptor NMDA type subunit 1;glutamate ionotropic receptor NMDA type subunit 2B;HIVEP zinc finger 2;intersectin 1;potassium voltage-gated channel subfamily Q member 2;potassium voltage-gated channel subfamily Q member 5;myelin transcription factor 1 like;neurobeachin;kinesin family member 1A | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. C2C12 - Mouse myoblast cells. PC-3 - Human prostate cancer cells. | |
| 68 | Autosomal dominant omodysplasia | fewer than 50 cases reported in the medical literature worldwide | FZD2 | Frizzled-2 Fz-2 Hfz2 | Autosomal dominant omodysplasia is a rare genetic disorder characterized by distinctive skeletal abnormalities, particularly affecting the long bones in the arms and legs (humerus and femur). Individuals with this condition often have short stature, shortened and bowed limbs, and characteristic facial features such as a prominent forehead, midface hypoplasia, and a broad nasal bridge. The condition is inherited in an autosomal dominant manner, meaning a single copy of the altered gene in each cell is sufficient to cause the disorder. Mutations in the gene GPC6 are commonly associated with autosomal dominant omodysplasia. | frizzled class receptor 2 | HEK293-Human embryonic kidney cells HCT116 -Human colon cancer cells IMR-90-Human lung fibroblast cells Rat-1-Rat fibroblast cell lines RLE-6TN-Rat lung epithelial cells Rat smooth muscle cells | |
| 69 | Autosomal dominant osteopetrosis type 1 | approximately 1 in 20,000 individuals | LRP5 | LR3 LRP-5 HBM (High Bone Mass) BMND1 (Bone Mass Density 1) EVR1 (Exudative Vitreoretinopathy 1) OPPG (Osteoporosis-Pseudoglioma Syndrome) | Autosomal dominant osteopetrosis type 1 (ADO1), also known as osteopetrosis tarda, is a rare genetic disorder characterized by increased bone density and abnormal bone growth. Unlike other forms of osteopetrosis, ADO1 is typically less severe and presents later in life, often during adolescence or adulthood. The disorder results from mutations in the LRP5 gene, which plays a crucial role in bone metabolism. Symptoms may include fractures, scoliosis, osteoarthritis, and bone pain. Diagnosis is usually confirmed through radiographic imaging and genetic testing. Treatment focuses on managing symptoms and preventing complications. | LDL receptor related protein 5 | MG-63-Human osteoblast cells HEK293-Human embryonic kidney cells HCT116 -Human colorectal cancer cells UMR-106 -Rat osteoblast cells Rat mesenchymal stem cells (MSCs) Rat-1 -Rat fibroblast cell lines | |
| 70 | Autosomal dominant polycystic kidney disease | 1 in 400 to 1 in 1,000 individuals worldwide | ALG9;DNAJB11;BICC1;GANAB;IFT140;PKD2;PKD1 | ALG9 (Alpha-1,2-Mannosyltransferase ALG9) Alias: AAG9, ALG9A, CDG-IL, DPAGT4, DIBD1 DNAJB11 (DnaJ Heat Shock Protein Family (Hsp40) Member B11) Alias: ERdj3, HSJ-2, HSPF5 BICC1 (BicC Family RNA Binding Protein 1) Alias: BICC, FLJ20441, MGC19598 GANAB (Glucosidase II Alpha Subunit) Alias: GIIalpha, GCS2, GANB IFT140 (Intraflagellar Transport 140 Homolog) Alias: CILD16, FLJ20474, THM1 PKD2 (Polycystin 2, Transient Receptor Potential Cation Channel) Alias: APKD2, Polycystin-2, TRPP2 PKD1 (Polycystin 1, Transient Receptor Potential Cation Channel) Alias: APKD1, PBP, PC1 | Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of numerous fluid-filled cysts in the kidneys. It is caused by mutations in either the PKD1 or PKD2 gene, leading to abnormal proliferation of renal tubular epithelial cells and cyst formation. ADPKD is inherited in an autosomal dominant pattern, meaning that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. Symptoms typically manifest in adulthood and may include abdominal pain, hypertension, hematuria, and renal impairment. ADPKD is one of the most common inherited kidney disorders and is a leading cause of end-stage renal disease (ESRD) worldwide. Management focuses on symptom relief, preservation of renal function, and addressing complications such as hypertension and cyst infections. | ALG9 alpha-1,2-mannosyltransferase;DnaJ heat shock protein family (Hsp40) member B11;BicC family RNA binding protein 1;glucosidase II alpha subunit;intraflagellar transport 140;polycystin 2, transient receptor potential cation channel;polycystin 1, transient receptor potential channel interacting | HEK293-Human embryonic kidney cells HepG2 -Human liver cancer cells HCT116-Human colorectal cancer cells Human renal proximal tubular cells ARPE-19-Human retinal pigment epithelial cells Human fibroblast cells (often derived from patients with ciliopathies) Rat hepatocyte cells ( primary rat liver cells) Rat-1-Rat fibroblast cells NRK-52E-Rat kidney cells | |
| 71 | Autosomal dominant primary microcephaly | 1 in 10,000 to 1 in 250,000 births | LMNB1;DPP6 | LMNB1 (Lamin B1) Alias: LMN2, LMNB DPP6 (Dipeptidyl-Peptidase 6) Alias: DPPX, Dipeptidyl peptidase-like protein 6 | Autosomal dominant primary microcephaly (MCPH) is a rare genetic disorder characterized by significantly reduced head size at birth and impairment in brain development, leading to intellectual disability and developmental delays. It is inherited in an autosomal dominant pattern, meaning that one copy of the altered gene in each cell is sufficient to cause the disorder. Mutations in several genes, including ASPM, CDK5RAP2, and WDR62, among others, have been associated with MCPH. The severity of symptoms can vary, but affected individuals typically have mild to moderate intellectual disability and may experience other neurological abnormalities. Early diagnosis through genetic testing and supportive interventions are essential for managing the condition and optimizing outcomes. | lamin B1;dipeptidyl peptidase like 6 | HEK293-Human embryonic kidney cells NIH 3T3 -Human fibroblast cells HeLa-Human cancer cell lines Rat-1 -Rat fibroblast cell lines PC12 -Rat neuroblastoma cells | |
| 72 | Autosomal dominant severe congenital neutropenia | 1 in 200,000 to 1 in 1 million individuals worldwide | SRP54;CLPB;TCIRG1;GFI1;ELANE | SRP54 (Signal Recognition Particle 54) Alias: SRP54, SRP54P, Ffh, SRP54M CLPB (Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit B) Alias: CLPB, MGC:5166, ATP-dependent Clp protease ATP-binding subunit ClpB TCIRG1 (T Cell Immune Regulator 1, ATPase H+ Transporting V0 Subunit A3) Alias: TCIRG1, OSTM1, OC-116KDa, a3, a3V-ATPase, OSTM1 GFI1 (Growth Factor Independent 1 Transcriptional Repressor) Alias: GFI1, GFI-1, GFI1B ELANE (Elastase, Neutrophil Expressed) Alias: ELANE, HLE, NE, SCN1, ELA2 | Autosomal dominant severe congenital neutropenia (ADSCN) is a rare inherited disorder characterized by abnormally low levels of neutrophils, a type of white blood cell essential for fighting off bacterial infections. In ADSCN, affected individuals typically experience recurrent and severe bacterial infections starting from early childhood. The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene from either parent is sufficient to cause the disorder. Mutations in genes such as ELANE (encoding elastase) and HAX1 (encoding HCLS1-associated protein X-1) are commonly associated with ADSCN. Treatment often involves the use of granulocyte colony-stimulating factor (G-CSF) to stimulate neutrophil production and reduce the frequency of infections. Bone marrow transplantation may be considered in severe cases. Early diagnosis and management are crucial for improving outcomes in individuals with ADSCN. | signal recognition particle 54;caseinolytic mitochondrial matrix peptidase chaperone subunit B;T cell immune regulator 1, ATPase H+ transporting V0 subunit a3;growth factor independent 1 transcriptional repressor;elastase, neutrophil expressed | HEK293-Human embryonic kidney cells HCT116-Human colon cancer cells HepG2-Human liver cells Rat-1 -Rat fibroblast cell lines PC12 - Rat neuroblastoma cells Rat liver cells (e.g., primary rat hepatocytes) | |
| 73 | Autosomal erythropoietic protoporphyria | 1 to 9 cases per 1 million individuals worldwide | FECH | Ferrochelatase Protoporphyrin ferrochelatase Heme synthetase FEC | Autosomal erythropoietic protoporphyria (EPP) is a rare genetic disorder characterized by the impaired function of an enzyme called ferrochelatase, leading to the accumulation of protoporphyrin in the body, particularly in the bone marrow, blood, and skin. When exposed to sunlight, this excess protoporphyrin can cause painful photosensitivity reactions, including burning, itching, and swelling of the skin. EPP is inherited in an autosomal recessive manner, meaning that affected individuals inherit two mutated copies of the gene associated with the disorder, one from each parent. Management typically involves avoiding sunlight exposure and using protective clothing and sunscreen to minimize symptoms. | ferrochelatase | ||
| 74 | Autosomal recessive Alport syndrome | less than 1 in 100,000 individuals | COL4A4;COL4A3 | COL4A4 (Collagen Type IV Alpha 4 Chain) Alias: Goodpasture antigen-related protein, GBM2, Goodpasture syndrome antigen-related protein, GPAB COL4A3 (Collagen Type IV Alpha 3 Chain) Alias: BM143, Collagen alpha-3(IV) chain, BM600, Collagen IV alpha-3 chain, Goodpasture antigen-related protein, GBM1 | Autosomal recessive Alport syndrome is a genetic disorder characterized by kidney disease, hearing loss, and eye abnormalities. It is caused by mutations in genes involved in the production of type IV collagen, a key component of the basement membranes in the kidneys, ears, and eyes. Unlike the more common X-linked Alport syndrome, which primarily affects males, autosomal recessive Alport syndrome affects both males and females equally. Symptoms typically appear in childhood or early adulthood and can vary in severity. Kidney failure is a common complication, often requiring dialysis or kidney transplantation. Treatment focuses on managing symptoms and slowing the progression of kidney disease. | collagen type IV alpha 4 chain;collagen type IV alpha 3 chain | ||
| 75 | Autosomal recessive centronuclear myopathy | 1 in 50,000 to 1 in 200,000 individuals | RYR1;SPEG;TTN;BIN1 | RYR1 (Ryanodine Receptor 1) Alias: Ryanodine receptor 1, Malignant hyperthermia 1 SPEG (Striated Muscle Preferentially Expressed Protein Kinase) Alias: Striated muscle enriched protein kinase, FLJ11812, KIAA1313 TTN (Titin) Alias: Connectin, CMD1G, CMH9, TMD BIN1 (Bridging Integrator 1) Alias: Amphiphysin II, Myc box-dependent-interacting protein 1, SH3P9, CNM7 | Autosomal recessive centronuclear myopathy (ARCNM) is a rare genetic muscle disorder characterized by muscle weakness and wasting, particularly affecting muscles involved in movement and posture. It is caused by mutations in genes associated with muscle cell structure and function, such as the DNM2, BIN1, RYR1, and TTN genes. Symptoms typically manifest in infancy or early childhood and may include difficulties with motor skills, muscle weakness, respiratory problems, and delayed motor development. Diagnosis is usually made through genetic testing and muscle biopsy. Treatment focuses on managing symptoms and may include physical therapy, respiratory support, and other supportive measures. | ryanodine receptor 1;striated muscle enriched protein kinase;titin;bridging integrator 1 | ||
| 76 | Autosomal recessive cerebellar ataxia-movement disorder syndrome | 1–2.5/100,000 | VPS13D;VPS41 | VPS13D (Vacuolar Protein Sorting 13 Homolog D) Alias: CHAC, COH1, C9orf15, Vacuolar Protein Sorting 13D VPS41 (Vacuolar Protein Sorting 41 Homolog) Alias: C13orf12, hVPS41, Vacuolar Protein Sorting 41 | Autosomal recessive cerebellar ataxia-movement disorder syndrome (ARCA-MD) is a genetic disorder characterized by progressive cerebellar ataxia, which affects coordination and balance, along with various movement abnormalities. It typically manifests in childhood or adolescence. The syndrome encompasses a group of disorders with overlapping features, including impaired motor coordination, tremors, dystonia, and sometimes cognitive impairment. Mutations in various genes involved in cerebellar function and movement control contribute to the heterogeneous nature of ARCA-MD. Management often involves supportive care and symptomatic treatment, though research into targeted therapies is ongoing. | vacuolar protein sorting 13 homolog D;VPS41 subunit of HOPS complex | ||
| 77 | Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form | 1 in 200,000 to 1 in 500,000 births globally | COL7A1 | EBA1 (Epidermolysis Bullosa, Dystrophic, Autosomal Recessive, Type IA) EBS1 (Epidermolysis Bullosa, Simplex, Dowling-Meara Type) KDEB1 (Kohlschütter-Tönz Syndrome) DEB (Dystrophic Epidermolysis Bullosa) EBS (Epidermolysis Bullosa Simplex) EDA (Epidermolysis Bullosa, Autosomal Dominant, Localized) MEDR (Medial Orbital Fibromatosis with Epidermolysis Bullosa) NBC1 (Naevus Butterfly Type, with Epidermolysis Bullosa) | Autosomal recessive generalized dystrophic epidermolysis bullosa (RDEB) is a severe genetic skin disorder characterized by blistering and erosions of the skin and mucous membranes. The intermediate form of RDEB lies between the severe and mild forms in terms of disease severity. In this intermediate subtype, blistering tends to occur at or shortly after birth, but may improve with age. However, individuals with the intermediate form still experience significant skin fragility, scarring, and complications such as impaired wound healing, joint contractures, and potential involvement of internal organs. RDEB is caused by mutations in the COL7A1 gene, which encodes type VII collagen, a crucial component of anchoring fibrils that attach the epidermis to the underlying dermis. Treatment primarily focuses on wound care, pain management, nutritional support, and prevention of complications. | collagen type VII alpha 1 chain | COS-7 - Monkey kidney fibroblast cells. Kera - Human keratinocytes (used in studies of skin biology). HDF - Human dermal fibroblasts | |
| 78 | Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form | 1 in 300,000 to 1 in 600,000 live births worldwide | MMP1;COL7A1 | " EBA1 (Epidermolysis Bullosa, Dystrophic, Autosomal Recessive, Type IA) EBS1 (Epidermolysis Bullosa, Simplex, Dowling-Meara Type) KDEB1 (Kohlschütter-Tönz Syndrome) DEB (Dystrophic Epidermolysis Bullosa) EBS (Epidermolysis Bullosa Simplex) EDA (Epidermolysis Bullosa, Autosomal Dominant, Localized) MEDR (Medial Orbital Fibromatosis with Epidermolysis Bullosa) NBC1 (Naevus Butterfly Type, with Epidermolysis Bullosa)" | Autosomal recessive generalized dystrophic epidermolysis bullosa (RDEB) is a severe genetic skin disorder characterized by blistering and erosions of the skin and mucous membranes in response to minor trauma or friction. It results from mutations in the COL7A1 gene, which encodes type VII collagen, a crucial protein for anchoring the skin layers together. In severe cases, patients experience widespread blistering, scarring, and deformities, leading to significant morbidity and mortality. Treatment focuses on wound care, infection prevention, and symptomatic management, as there is currently no cure for RDEB. | matrix metallopeptidase 1;collagen type VII alpha 1 chain | ||
| 79 | Autosomal recessive hypohidrotic ectodermal dysplasia | 1 in 100,000 births | EDARADD;WNT10A;EDAR;CSTB | EDARADD (EDAR-Associated Death Domain) Alias: EDARADD, ED1R-associated death domain WNT10A (Wnt Family Member 10A) Alias: WNT10A, HID, WNT12 EDAR (Ectodysplasin A Receptor) Alias: EDAR, ECTOD1, DL, ECTD1, HED CSTB (Cystatin B) Alias: CSTB, CST6, EPM1, STFB | Autosomal recessive hypohidrotic ectodermal dysplasia (AR-HED) is a rare genetic disorder characterized by abnormalities in the development of ectodermal structures such as skin, hair, teeth, and sweat glands. It is caused by mutations in genes such as EDA, EDAR, or EDARADD, which play crucial roles in the ectodermal development pathway. Individuals with AR-HED typically present with sparse or absent hair, missing or malformed teeth, and reduced ability to sweat, which can lead to overheating. Other features may include dry skin, abnormal nails, and respiratory problems due to abnormal development of the airway. The severity of symptoms can vary widely among affected individuals. Management of AR-HED involves addressing the symptoms through various interventions such as dental prosthetics for missing teeth, artificial sweat production methods, and skincare to manage dry skin. Genetic counseling is important for affected individuals and their families to understand the inheritance pattern and recurrence risk. | EDAR associated death domain;Wnt family member 10A;ectodysplasin A receptor;cystatin B | COS-7 - Monkey kidney fibroblast cells. A549 - Human lung carcinoma cells. HeLa - Human cervical cancer cells. | |
| 80 | Autosomal recessive omodysplasia | less than 40 cases of omodysplasia have been described in the literature so far | GPC6 | DCDG-1 (Developmentally regulated GPC6) GPC6D (Glypican-6D) GYPC6 (Glypican 6) DKFZp686D01152 (a name used in some databases and annotations) | Autosomal recessive omodysplasia is a rare genetic disorder characterized by skeletal abnormalities such as short stature, bowed legs, and a small chest. It is caused by mutations in the LTBP3 gene, which plays a role in the development and maintenance of bone and connective tissue. This condition is inherited in an autosomal recessive manner, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to manifest the disorder. Symptoms may vary in severity among affected individuals, and management typically involves supportive care to address the specific symptoms and complications associated with the condition. | glypican 6 | HeLa - Human cervical cancer cells. PC-3 - Human prostate cancer cells. COS-7 - Monkey kidney fibroblast cells. | |
| 81 | Autosomal recessive primary microcephaly | approximately 1 in 10,000 to 1 in 250,000 live births worldwide | KNL1;COPB2;CIT;KIF14;PHC1;CDK5RAP2;CDK6;CENPJ;TAF13;STIL;TRAPPC14;CEP63;MFSD2A;WDR62;METTL5;SASS6;ASPM;MCPH1;PYCR2;CEP152;ANKLE2;CEP135;NCAPD3 | KNL1 (Kinetochore Scaffold 1) Alias: CASC5, Blinkin COPB2 (COPI Coat Complex Subunit Beta 2) Alias: Beta-COP CIT (Citron Rho-Interacting Serine/Threonine Kinase) Alias: Citron kinase KIF14 (Kinesin Family Member 14) Alias: KNSL2, KIF14B PHC1 (Polyhomeotic Homolog 1) Alias: BMI1, RING1B CDK5RAP2 (CDK5 Regulatory Subunit Associated Protein 2) Alias: CEP215 CDK6 (Cyclin Dependent Kinase 6) Alias: None CENPJ (Centromere Protein J) Alias: CPAP TAF13 (TATA-Box Binding Protein Associated Factor 13) Alias: None STIL (STIL Centriolar Assembly Protein) Alias: SIL, SCL/TAL1 Interrupting Locus TRAPPC14 (Trafficking Protein Particle Complex Subunit 14) Alias: TRS130 CEP63 (Centrosomal Protein 63) Alias: None MFSD2A (Major Facilitator Superfamily Domain Containing 2A) Alias: None WDR62 (WD Repeat Domain 62) Alias: KIAA1570 METTL5 (Methyltransferase Like 5) Alias: None SASS6 (SAS-6 Centriolar Assembly Protein) Alias: None ASPM (Abnormal Spindle Microtubule Assembly) Alias: MCPH5, MCPH, MGC111025 MCPH1 (Microcephalin 1) Alias: BRIT1, BRCT-repeat inhibitor of hTERT expression, Microcephalin PYCR2 (Pyrroline-5-Carboxylate Reductase Family Member 2) Alias: None CEP152 (Centrosomal Protein 152) Alias: None ANKLE2 (Ankyrin Repeat And LEM Domain Containing 2) Alias: KIAA1154 CEP135 (Centrosomal Protein 135) Alias: None NCAPD3 (Non-SMC Condensin II Complex Subunit D3) Alias: hCAP-D3, KIAA0154 | Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder characterized by significantly reduced head size at birth and impaired brain development, leading to intellectual disability and developmental delays. It is inherited in an autosomal recessive pattern, meaning both copies of the responsible gene (usually ASPM, WDR62, or other related genes) must be mutated for the condition to manifest. Individuals with MCPH typically have normal body proportions and no other major physical abnormalities. The severity of symptoms can vary, but affected individuals often face challenges in cognitive function, motor skills, and speech development. Treatment primarily focuses on supportive care and early intervention programs to maximize developmental outcomes. | |||
| 82 | Autosomal recessive spastic ataxia of Charlevoix-Saguenay | 1 in 1,500 to 1 in 2,000 individuals | SACS | SACS SACsin ARSA Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay SPAX6 | Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by a triad of symptoms: spasticity (stiffness and involuntary muscle spasms), ataxia (lack of muscle coordination), and peripheral neuropathy (damage to nerves outside the brain and spinal cord). It is caused by mutations in the SACS gene and typically manifests in early childhood. Symptoms worsen over time, leading to progressive disability. ARSACS is primarily found in individuals of French-Canadian descent, particularly those from the Charlevoix-Saguenay-Lac-Saint-Jean region of Quebec, though cases have been reported in other populations. There is currently no cure for ARSACS, and treatment focuses on managing symptoms and providing supportive care. | sacsin molecular chaperone | NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. COS-7 - Monkey kidney fibroblast cells. PC12 - Rat pheochromocytoma cells. | |
| 83 | Autosomal recessive spastic ataxia-optic atrophy-dysarthria syndrome | 1 to 5 cases per 100,000 individuals | MTPAP | MT-Poly(A) Polymerase PAPD1 (Poly(A) Polymerase Delta 1) MitoPLD (Mitochondrial Poly(A) Polymerase) POLRMT2L (Polymerase (RNA) Mitochondrial (DNA-Directed) Catalytic Subunit 2 Like) | Autosomal recessive spastic ataxia-optic atrophy-dysarthria (SPAX3) syndrome is a rare neurodegenerative disorder characterized by a combination of symptoms including progressive spasticity (stiffness and contraction of muscles), ataxia (lack of muscle coordination), optic atrophy (damage to the optic nerve leading to vision loss), and dysarthria (difficulty speaking due to impaired muscle control). This syndrome typically manifests in childhood or adolescence and progressively worsens over time. SPAX3 is caused by mutations in the TTPA gene, which encodes a protein involved in vitamin E metabolism. Treatment mainly focuses on managing symptoms and providing supportive care, as there is currently no cure for this condition. | mitochondrial poly(A) polymerase | ||
| 84 | Autosomal recessive spastic paraplegia type 11 | 1 to 2 per 1,000,000 individuals worldwide | SPG11 | KIAA1840 (KIAA1840 Gene) SPG11 Gene (Spastic Paraplegia 11 Gene) | Autosomal recessive spastic paraplegia type 11 (SPG11) is a rare neurodegenerative disorder characterized by progressive weakness and spasticity in the lower limbs, leading to difficulty walking. It typically begins in childhood or adolescence and worsens over time. SPG11 is caused by mutations in the SPG11 gene, which plays a role in maintaining the structure and function of nerve cells. Symptoms may also include intellectual disability, cognitive decline, and other neurological features. Treatment focuses on managing symptoms and supportive care, as there is currently no cure for SPG11. | SPG11 vesicle trafficking associated, spatacsin | ||
| 85 | Autosomal recessive spastic paraplegia type 15 | fewer than 1 in 1 million individuals worldwide | ZFYVE26 | SPG15 | Autosomal recessive spastic paraplegia type 15 (SPG15) is a rare neurological disorder characterized by progressive stiffness and weakness (spasticity) in the lower limbs. It is caused by mutations in the ZFYVE26 gene, which plays a role in regulating the transport of proteins within cells. Symptoms typically begin in childhood or adolescence and gradually worsen over time. In addition to spasticity, individuals with SPG15 may experience difficulty walking, muscle weakness, and may develop complications such as contractures or urinary problems. Treatment focuses on managing symptoms and may include physical therapy, medications to alleviate spasticity, and supportive care. | zinc finger FYVE-type containing 26 | N2A (Neuro-2a) - Mouse neuroblastoma cells. PC12 - Rat pheochromocytoma cells. COS-7 - Monkey kidney fibroblast cells. NIH 3T3 - Mouse fibroblast cells. | |
| 86 | Autosomal recessive spastic paraplegia type 23 | fewer than 1 in 1 million individuals globally | DSTYK | Autosomal recessive spastic paraplegia type 23 (SPG23) is a rare neurological disorder characterized by progressive weakness and stiffness (spasticity) in the muscles of the lower limbs. It is caused by mutations in the gene encoding the protein receptor expression-enhancing protein 1 (REEP1). This condition typically presents in childhood or adolescence and gradually worsens over time, leading to difficulties with walking and mobility. Additional symptoms may include muscle wasting, urinary urgency, and sensory abnormalities. Management typically involves supportive therapies to alleviate symptoms and improve quality of life, as there is currently no cure for SPG23. | dual serine/threonine and tyrosine protein kinase | PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. PC-3 - Human prostate cancer cells. NIH 3T3 - Mouse fibroblast cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. | ||
| 87 | Autosomal recessive spondylocostal dysostosis | 1 in 1,000,000 births | HES7;LFNG;RIPPLY2;DLL3;MESP2 | HES7: Alias: Hairy and Enhancer of Split 7 LFNG: Alias: Lunatic Fringe RIPPLY2: Alias: Ripply Transcriptional Repressor 2 DLL3: Alias: Delta-Like Canonical Notch Ligand 3 Alternative Name: Hensen's Node Streak-Associated Protein (HNAP) MESP2: Alias: Mesoderm Posterior BHLH Transcription Factor 2 | Autosomal recessive spondylocostal dysostosis (ARSD) is a rare genetic disorder characterized by abnormalities in the spine and ribs. It typically presents with vertebral segmentation defects, such as fusion or abnormal separation of vertebrae, leading to a short trunk and a barrel-shaped chest. This condition is inherited in an autosomal recessive manner, meaning both copies of the gene must be mutated for the disorder to manifest. ARSD can cause respiratory complications due to the restricted chest cavity and may be associated with other skeletal abnormalities. Early diagnosis and management by a multidisciplinary team are essential for optimizing outcomes in affected individuals. | hes family bHLH transcription factor 7;LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase;ripply transcriptional repressor 2;delta like canonical Notch ligand 3;mesoderm posterior bHLH transcription factor 2 | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. | |
| 88 | B-cell chronic lymphocytic leukemia | Its prevalence increases with age, with the median age at diagnosis being around 70 years old | IGHV3-21;ATM;P2RX7;CCND1;RPS15;ARL11;POT1;IKZF3;TP53;IGHG1 | IGHV3-21: IGHV3-21, Immunoglobulin heavy variable 3-21 ATM: ATM, Ataxia Telangiectasia Mutated P2RX7: P2RX7, Purinergic Receptor P2X, Ligand-Gated Ion Channel 7 CCND1: CCND1, Cyclin D1 BCL1, B-Cell CLL/Lymphoma 1 RPS15: RPS15, Ribosomal Protein S15 ARL11: ARL11, ADP-Ribosylation Factor Like GTPase 11 POT1: POT1, Protection of Telomeres 1 IKZF3: IKZF3, Ikaros Family Zinc Finger 3 AIOLOS, IKAROS family zinc finger 3 TP53: TP53, Tumor Protein P53 p53, Cellular tumor antigen p53 IGHG1: IGHG1, Immunoglobulin heavy constant gamma 1 IgG1, Immunoglobulin G1 | B-cell chronic lymphocytic leukemia (CLL) is a type of cancer that affects white blood cells called lymphocytes, specifically B cells. In CLL, abnormal lymphocytes accumulate in the blood, bone marrow, and lymphoid tissues, crowding out normal blood cells and impairing immune function. It is typically a slow-growing leukemia and may not cause symptoms in the early stages. Common symptoms include enlarged lymph nodes, fatigue, weight loss, and frequent infections. CLL is diagnosed through blood tests and bone marrow biopsy. Treatment options vary depending on the stage and progression of the disease, ranging from watchful waiting to chemotherapy, immunotherapy, and targeted therapies. | immunoglobulin heavy variable 3-21;ATM serine/threonine kinase;purinergic receptor P2X 7;cyclin D1;ribosomal protein S15;ADP ribosylation factor like GTPase 11;protection of telomeres 1;IKAROS family zinc finger 3;tumor protein p53;immunoglobulin heavy constant gamma 1 (G1m marker) | NIH 3T3 - Mouse fibroblast cells. HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. | |
| 89 | Bainbridge-Ropers syndrome | fewer than 100 cases reported in the medical literature | ASXL3 | KIAA1797 ASX-Like Protein 3 ASXL3. | Bainbridge-Ropers syndrome (BRPS) is a rare genetic disorder resulting from mutations in the ASXL3 gene. It manifests with a spectrum of developmental and physical abnormalities, including significant intellectual disability, delayed speech and motor milestones, and feeding challenges. Individuals with BRPS often exhibit distinct facial features such as a prominent forehead, arched eyebrows, and a downturned mouth, along with hypotonia (low muscle tone). Behavioral issues, including traits associated with autism spectrum disorder, are also common. Diagnosis is primarily achieved through genetic testing, and treatment is focused on managing the specific symptoms and providing supportive therapies to enhance the quality of life. | ASXL transcriptional regulator 3 | N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. HeLa - Human cervical cancer cells. A549 - Human lung carcinoma cells. | |
| 90 | Baller-Gerold syndrome | fewer than 50 cases reported in the medical literature worldwide | RECQL4 | RECQ4 RecQ protein-like 4 RECQ4 helicase RTS (Rothmund-Thomson syndrome gene) Rothmund-Thomson syndrome helicase SGS (subset of RAPADILINO syndrome gene) WRN3 (Werner syndrome, RecQ helicase-like 3) QDE3 (quelling deficient-3) DNA helicase Q4 | Baller-Gerold syndrome is a rare genetic disorder characterized by the combination of craniosynostosis (premature fusion of skull bones) and radial aplasia (absence or malformation of the radius bone in the forearm). Additional features can include growth retardation, distinctive facial features, and skeletal abnormalities. The condition is inherited in an autosomal recessive manner and is often associated with mutations in the RECQL4 gene, which plays a role in DNA repair and maintenance of genomic stability. | RecQ like helicase 4 | ||
| 91 | Band heterotopia | 1 in 100,000 to 1 in 1,000,000 individuals | EML1 | EMAP-115 EMAP115 ELP115 Echinoderm Microtubule Associated Protein Like 1 | Band heterotopia, also known as double cortex syndrome, is a rare neuronal migration disorder characterized by the presence of a band of grey matter located in the white matter, parallel to the cerebral cortex. This condition occurs due to a defect in the migration of neurons during brain development. It is often associated with epilepsy, intellectual disability, and developmental delays. Band heterotopia is usually linked to mutations in the DCX (doublecortin) gene, which is located on the X chromosome. It predominantly affects females, as the condition is often lethal in males who inherit the mutation. Diagnosis is typically made through imaging techniques like MRI, which reveals the characteristic double layer of cortex. | EMAP like 1 | ||
| 92 | Baraitser-Winter cerebrofrontofacial syndrome | < 1 / 1 000 000 | ACTB;ACTG1 | ACTB (Actin Beta): β-actin cytoplasmic actin gamma-actin F-actin, beta polypeptide ACTB actin, beta ACTG1 (Actin Gamma 1): γ-actin cytoplasmic actin 2 ACTG1 actin, gamma 1 cytoskeletal gamma-actin | Baraitser-Winter cerebrofrontofacial syndrome is a rare genetic disorder characterized by a distinct facial appearance, intellectual disability, and abnormalities of the brain and skull. Individuals with this syndrome typically have a prominent forehead, widely spaced eyes, small jaw, and a broad nasal bridge. They may also exhibit developmental delay, seizures, and structural brain anomalies such as abnormal folds or grooves. Baraitser-Winter syndrome is caused by mutations in genes associated with brain development, and its inheritance pattern is typically autosomal dominant. Due to its rarity, comprehensive understanding of the syndrome is still evolving. | actin beta;actin gamma 1 | ||
| 93 | Barber-Say syndrome | fewer than 1 in 1,000,000 individuals globally | TWIST2 | Dermo1-like protein Derml2 bHLHa39 TWIST-2 TWIST-related protein 2 Class A basic helix-loop-helix protein 39 | Barber-Say syndrome, also known as BSS, is an extremely rare genetic disorder characterized by distinctive facial features, such as sparse hair on the scalp, bushy eyebrows, prominent ears, and a broad nasal tip. Individuals with BSS may also exhibit intellectual disability, developmental delays, and skeletal abnormalities. This condition is caused by mutations in the TWIST2 gene, which plays a role in embryonic development. Management typically involves supportive care to address the specific needs of affected individuals | twist family bHLH transcription factor 2 | ||
| 94 | Bardet-biedl syndrome 10 | around 1 in 100,000 to 1 in 160,000 individuals worldwide | BBS10 | Bardet-Biedl syndrome 10 BARD1 BBS10A FLJ20203 C12orf58 | Bardet-Biedl syndrome (BBS) is a rare genetic disorder characterized by a wide range of symptoms that can affect various parts of the body. BBS is typically inherited in an autosomal recessive pattern, meaning both parents must pass on a defective gene for a child to develop the condition. BBS affects multiple systems of the body, leading to symptoms such as obesity, retinal degeneration causing vision loss, kidney abnormalities, intellectual disability, genital anomalies, and polydactyly (extra fingers or toes). Bardet-Biedl syndrome 10 (BBS10) is one of the known genetic subtypes of BBS, caused by mutations in the BBS10 gene. Mutations in this gene disrupt the function of cilia, which are microscopic hair-like structures found on the surface of cells and play crucial roles in various cellular processes. Individuals with BBS10 typically exhibit features consistent with BBS, such as obesity, vision problems, kidney abnormalities, and other associated symptoms. Management of BBS involves a multidisciplinary approach to address the various medical, developmental, and psychosocial aspects of the condition. | Bardet-Biedl syndrome 10 | N2A (Neuro-2a) - Mouse neuroblastoma cells. MCF-7 - Human breast cancer cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. | |
| 95 | Bardet-biedl syndrome 12 | around 1 in 100,000 to 1 in 160,000 individuals worldwide | BBS12 | Bardet-Biedl syndrome 10 BARD1 BBS10A FLJ20203 C12orf58 | "Bardet-Biedl syndrome (BBS) is a rare genetic disorder characterized by a wide range of symptoms that can affect various parts of the body. BBS is typically inherited in an autosomal recessive pattern, meaning both parents must pass on a defective gene for a child to develop the condition. BBS affects multiple systems of the body, leading to symptoms such as obesity, retinal degeneration causing vision loss, kidney abnormalities, intellectual disability, genital anomalies, and polydactyly (extra fingers or toes). Bardet-Biedl syndrome 10 (BBS10) is one of the known genetic subtypes of BBS, caused by mutations in the BBS10 gene. Mutations in this gene disrupt the function of cilia, which are microscopic hair-like structures found on the surface of cells and play crucial roles in various cellular processes. Individuals with BBS10 typically exhibit features consistent with BBS, such as obesity, vision problems, kidney abnormalities, and other associated symptoms. Management of BBS involves a multidisciplinary approach to address the various medical, developmental, and psychosocial aspects of the condition." | Bardet-Biedl syndrome 12 | N2A (Neuro-2a) - Mouse neuroblastoma cells. MCF-7 - Human breast cancer cells. NIH 3T3 - Mouse fibroblast cells. COS-7 - Monkey kidney fibroblast cells. | |
| 96 | Becker nevus syndrome | affects approximately 0.5-1% of the population | ACTB | ACTB (official symbol) β-actin Beta-actin ACTB1 PS1TP5BP1 BRWS1 Actin, beta cytoskeletal beta-actin actin, cytoplasmic 1 beta-actin-like protein 2 | Becker's nevus syndrome is a rare condition characterized by the presence of Becker's nevus, a large, irregularly shaped, pigmented birthmark often accompanied by coarse hair growth. Alongside the nevus, individuals may exhibit various features such as muscle, breast, or skeletal abnormalities on the same side of the body as the nevus. These abnormalities can vary widely in severity and presentation. Becker's nevus syndrome primarily affects males, though it can occur in females as well. The exact cause of the syndrome is unknown, but it's believed to involve a combination of genetic and hormonal factors. Treatment options typically focus on managing the cosmetic appearance of the nevus and addressing any associated complications. | actin beta | PC12 - Rat pheochromocytoma cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. NIH 3T3 - Mouse fibroblast cells. | |
| 97 | Benign recurrent intrahepatic cholestasis type 1 | 1 in 100,000 to 200,000 individuals | ATP8B1 | FIC1 ATPICD ATPICDNL ATPase, Class I, Type 8B, Member 1 P4-ATPase flippase complex alpha subunit ATP8B1 FIC1P MDR3 | Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is a rare genetic disorder characterized by recurrent episodes of liver dysfunction. It typically begins in childhood or early adulthood. BRIC1 is caused by mutations in the ATP8B1 gene, which is involved in bile secretion. These mutations impair the normal flow of bile from the liver, leading to symptoms such as severe itching, jaundice, and fatigue during episodes. In between episodes, liver function may return to normal. Treatment primarily focuses on managing symptoms, such as with medications to relieve itching, but liver transplantation may be necessary in severe cases. | ATPase phospholipid transporting 8B1 | ||
| 98 | Beta-mannosidosis | fewer than 1 in 1 million individuals globally | MANBA | Beta-mannosidase Lysosomal beta-mannosidase Beta-D-mannosidase EC 3.2.1.25 (Enzyme Commission number) | Beta-mannosidosis is a rare inherited metabolic disorder characterized by a deficiency in the enzyme beta-mannosidase, which is responsible for breaking down complex sugar molecules in the body. This deficiency leads to the accumulation of mannose-containing oligosaccharides in various tissues and organs, resulting in a range of symptoms including developmental delay, intellectual disability, hearing loss, skeletal abnormalities, facial dysmorphism, and recurrent infections. The severity of symptoms can vary widely among affected individuals. Beta-mannosidosis follows an autosomal recessive pattern of inheritance, meaning that individuals must inherit two copies of the defective gene (one from each parent) to develop the disorder. Treatment options are currently limited and mainly focus on managing symptoms and providing supportive care. | mannosidase beta | N2A (Neuro-2a) - Mouse neuroblastoma cells. SH-SY5Y - Human neuroblastoma cells. A549 - Human lung carcinoma cells. COS-7 - Monkey kidney fibroblast cells. | |
| 99 | Bilateral multicystic dysplastic kidney | around 1 in 4,300 live births | HNF1B | TCF2 (Transcription Factor 2) LFB1 (Liver-specific Factor 1) MODY5 (Maturity-Onset Diabetes of the Young 5) LF-B1 (Liver Factor B1) TCF-2 (Transcription Factor 2) VHNF1 (Variant Hepatocyte Nuclear Factor 1) | Bilateral multicystic dysplastic kidney (BMDK) is a congenital condition where both kidneys develop multiple cysts of varying sizes instead of normal kidney tissue. This results in non-functional kidneys that are unable to filter waste from the blood or produce urine. BMDK is typically diagnosed prenatally or in infancy through imaging studies. It is considered a rare condition and may be associated with other anomalies or genetic syndromes. Treatment involves managing associated complications and often includes renal replacement therapy such as dialysis or kidney transplantation. | HNF1 homeobox B | HEK293-Human embryonic kidney cells HepG2-Human liver cells RPTEC/TERT1-Human renal proximal tubular epithelial cells NRK-52E-Rat kidney epithelial cells | |
| 100 | Bloom syndrome | 1 in 48,000 to 1 in 1,000,000 individuals worldwide | BLM | RECQL2 (RecQ Like Helicase 2) BS (Bloom Syndrome protein) RECQ3 (RecQ DNA helicase 3) RECQ2 (RecQ DNA helicase 2) BLMC (Bloom Syndrome protein) RECQL3 (RecQ Like Helicase 3) | Bloom syndrome is a rare autosomal recessive disorder characterized by short stature, sun-sensitive skin changes, and a predisposition to various cancers. It results from mutations in the BLM gene, which is involved in DNA repair. Individuals with Bloom syndrome typically exhibit growth deficiency, a high-pitched voice, and a characteristic facial appearance. They are also prone to developing cancers at an early age, particularly leukemia and lymphoma, as well as solid tumors like colon, breast, and ovarian cancer. Bloom syndrome is inherited in an autosomal recessive manner, meaning both parents must carry a copy of the mutated gene for a child to inherit the disorder. | BLM RecQ like helicase | HEK293-Human embryonic kidney cells BJ-Human fibroblasts HeLa-Human cancer cell lines Rat-1-Rat fibroblasts PC12-Rat neuroblastoma cells | |
| 101 | Blue rubber bleb nevus | less than 1 in 200,000 individuals | TEK | TIE2 VMCM CD202B | Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by the presence of multiple vascular lesions, known as rubbery blue nodules or blebs, on the skin and internal organs. These lesions are composed of abnormal blood vessels and can cause various symptoms depending on their location, such as gastrointestinal bleeding, anemia, and pain. BRBNS is typically present from birth or develops early in childhood. It is caused by mutations in the TEK gene, which plays a role in blood vessel formation. Treatment may involve managing symptoms and, in some cases, surgical removal of problematic lesions. | TEK receptor tyrosine kinase | ARPE-19-Human retinal pigment epithelial cells HEK293-Human embryonic kidney cells NIH 3T3-Human fibroblasts Rat retinal cells (e.g., primary rat retinal cells or cell lines) Rat-1-Rat fibroblast cells | |
| 102 | Boomerang dysplasia | less than 1 in 1 million births | FLNB | FLN2 FLN-B ABP-278 TABP FH1 FLN2L MPD4 N-RAP | Boomerang dysplasia is an extremely rare skeletal disorder characterized by severe bone abnormalities, typically evident on prenatal ultrasound or shortly after birth. It is named for the characteristic boomerang-shaped bowed femurs seen in affected individuals. Other features may include short limbs, abnormal ossification of bones, and underdeveloped or absent bones in the hands and feet. Boomerang dysplasia is usually lethal either before or shortly after birth due to respiratory insufficiency caused by thoracic abnormalities. The genetic cause of this condition is not fully understood, but it is believed to be inherited in an autosomal dominant manner with variable expressivity. Due to its rarity, management typically focuses on supportive care. | filamin B | HeLa cells: human cervical cancer cells U2OS: human osteosarcoma cell line Endothelial cells: Expression is observed in cells involved in blood vessel formation. Rat primary osteoblasts: osteoblast cells. Rat vascular smooth muscle cells (VSMCs) Rat fibroblasts | |
| 103 | Bowen-Conradi syndrome | fewer than 1 in 1,000,000 individuals worldwide | EMG1 | MGC52498 EMG1 N-terminal domain-containing protein Essential for mitotic growth protein 1 60S ribosomal subunit assembly protein 1 Nucleolar protein EMG1 homolog | Bowen-Conradi syndrome is a rare genetic disorder characterized by severe growth and developmental delays, distinctive facial features, and various physical abnormalities. It is an autosomal recessive condition most commonly found in individuals of Hutterite ancestry. The syndrome is caused by mutations in the EMG1 gene, which plays a crucial role in ribosome biogenesis. Affected individuals often have a small head, prominent nose, micrognathia (small jaw), and significant feeding difficulties. Most children with Bowen-Conradi syndrome do not survive beyond infancy due to complications such as severe failure to thrive and respiratory issues. | EMG1 N1-specific pseudouridine methyltransferase | HeLa cells: Cervical cancer cell lines HEK293 cells: Human embryonic kidney cellsMCF-7 cells: A breast cancer cell line Rat hepatocytes: Primary liver cells Rat neural progenitor cells Rat fibroblasts: role in ribosome production | |
| 104 | Brachydactyly-arterial hypertension syndrome | fewer than 100 cases reported in the medical literature worldwid | PDE3A1 | CGI-PDE A Cyclic GMP-inhibited phosphodiesterase A cGIPDE cGI-PDE CGI-PDE | Brachydactyly-arterial hypertension syndrome is a rare genetic disorder characterized by the combination of shortened digits (brachydactyly) and high blood pressure (arterial hypertension). This syndrome is caused by mutations in the PDE3A gene, which encodes an enzyme involved in the regulation of vascular tone and bone development. Individuals with this condition typically exhibit short fingers and toes and may develop hypertension at a young age, which can increase the risk of cardiovascular complications. The syndrome is inherited in an autosomal dominant pattern. Management usually involves monitoring and treating hypertension to reduce associated health risks. | phosphodiesterase 3A | PC-3 - Human prostate cancer cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. COS-7 - Monkey kidney fibroblast cells. | |
| 105 | Branchioskeletogenital syndrome | fewer than 20 reported cases in the medical literature | CDH11 | OSF-4 (Osteoblast-specific factor 4) OB-cadherin (Osteoblast-cadherin) Cadherin-11 | Branchioskeletogenital syndrome, also known as Wildervanck-Smith syndrome, is an extremely rare genetic disorder characterized by a combination of branchial, skeletal, and genital anomalies. Individuals with this syndrome may exhibit branchial cysts, fistulas, or sinuses; skeletal malformations such as cervical vertebrae fusion (Klippel-Feil anomaly); and genital anomalies including ambiguous genitalia. Diagnosis is primarily based on clinical features, and genetic testing may be used for confirmation. Management typically involves a multidisciplinary approach to address the diverse physical anomalies present from birth. | phosphodiesterase 3A | PC-3 - Human prostate cancer cells. N2A (Neuro-2a) - Mouse neuroblastoma cells. PC-3 - Human prostate cancer cells. A549 - Human lung carcinoma cells. COS-7 - Monkey kidney fibroblast cells. | |
| 106 | Breast-ovarian cancer, familial, susceptibility to, 1 | 1 in 400 to 1 in 500 in the general population | BRCA1 | BRCC1 (Breast Cancer, early onset 1) BROVCA1 (Breast-ovarian cancer susceptibility gene 1) PSCP (PPP1R53) RNF53 (Ring Finger Protein 53) IRIS (Increased Reactivity to Ionizing Radiation) | Breast-ovarian cancer, familial, susceptibility to, 1, is primarily associated with mutations in the BRCA1 gene. This condition significantly increases the risk of developing breast and ovarian cancers at an early age, often before age 50. BRCA1 is a tumor suppressor gene, and mutations lead to impaired DNA repair, resulting in increased cancer risk. Inheritance is autosomal dominant, meaning a mutation in one copy of the gene can increase cancer susceptibility. Genetic testing for BRCA1 mutations can help identify at-risk individuals and guide preventive measures. | BRCA1 DNA repair associated | A549 - Human lung carcinoma cells. COS-7 - Monkey kidney fibroblast cells. | |
| 107 | Brugada syndrome 3 | 1 in 2,000 to 1 in 5,000 people worldwid | CACNA1C | Cav1.2 CACN2 CACNL1A1 CCHL1A1 LQT8) | Brugada syndrome 3 is a genetic disorder characterized by an increased risk of sudden cardiac death due to ventricular arrhythmias. It is one of several forms of Brugada syndrome, which is a condition that affects the heart's electrical system. Brugada syndrome 3 is specifically associated with mutations in the SCN5A gene, which encodes a sodium channel critical for cardiac electrical activity. The hallmark of the syndrome is a distinctive pattern on an electrocardiogram (ECG), known as a type 1 Brugada ECG pattern, which shows ST-segment elevation in the right precordial leads (V1-V3). This condition can lead to fainting, palpitations, and potentially fatal arrhythmias, often triggered by fever, certain medications, or electrolyte imbalances. Diagnosis is based on clinical criteria and ECG findings, and management may include lifestyle modifications, medication, and in some cases, the implantation of a cardioverter-defibrillator (ICD). | calcium voltage-gated channel subunit alpha1 | PC12 (rat pheochromocytoma) cells. H9c2 (rat cardiomyoblast) cells. SH-SY5Y (human neuroblastoma) cells. | |
| 108 | Brugada syndrome 4 | CACNB2 | Brugada syndrome is characterized by cardiac conduction abnormalities (ST-segment abnormalities in leads V1-V3 on ECG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and the sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome. | calcium voltage-gated channel auxiliary subunit beta 2 | HEK293 cells: Widely used for studies involving ion channels SH-SY5Y cells: Human neuroblastoma cells Cardiomyocytes (iPSC-derived): Induced pluripotent stem cells (iPSCs) H9c2 cells: Human heart muscle cells H9c2 cells: These are rat cardiomyoblasts (heart cells), PC12 cells: A rat pheochromocytoma cell line Rat primary neurons: Isolated neurons from rat brain tissue Rat vascular smooth muscle cells (VSMCs) | |||
| 109 | Burkitt lymphoma | MYC | Burkitt lymphoma (BL) is an aggressive non-Hodgkin B-cell lymphoma. The disease is associated with Epstein Barr virus (EBV), human immunodeficiency virus (HIV), and chromosomal translocations that cause the overexpression of oncogene c-myc.The World Health Organization (WHO) classifies BL into three clinical groups: endemic, sporadic and immunodeficiency-related. The endemic form is linked to malaria and EBV. The immunodeficiency-related variant is associated with HIV and to a lesser extent, organ transplantation. | MYC proto-oncogene, bHLH transcription factor | NIH/3T3 (mouse fibroblast) cells. A549 (human lung carcinoma) cells. HeLa (human cervical cancer) cells. A549 (human lung carcinoma) cells. | |||
| 110 | CAD-CDG | CAD | CAD-CDG is a rare condition that is often diagnosed during infancy. It is caused by changes in a gene called CAD that block an important step involving the sugar glycan. Glycan is needed by the cells and tissues that make up the body. As a result, this condition causes a wide range of health problems. Some common symptoms include seizures, global developmental delay (problems with learning and development), and problems with red blood cells. Red blood cell disorders that can occur with CAD-CDG include anemia (a low number of red blood cells) and anisopoikilocytosis (red blood cells of varying sizes and shapes). Signs and symptoms of CAD-CDG can worsen with time and result in life threatening complications. | carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase | HeLa cells: its role in pyrimidine synthesis. HEK293 cells: Human embryonic kidney cells HepG2 cells: A human liver carcinoma cell line MCF-7 cells: This breast cancer cell line Rat hepatocytes: Primary liver cells Rat fibroblasts PC12 cells: Rat pheochromocytoma cells Rat primary neurons: Neurons from rat brain tissue | |||
| 111 | Calpain-3-related limb-girdle muscular dystrophy R1 | CAPN3 | A subtype of autosomal recessive limb girdle muscular dystrophy characterized by a variable age of onset of progressive, typically symmetrical and selective weakness and atrophy of proximal shoulder- and pelvic-girdle muscles (gluteus maximus, thigh adductors, and muscles of the posterior compartment of the limbs are most commonly affected) without cardiac or facial involvement. Clinical manifestations include exercise intolerance, a waddling gait, scapular winging and calf pseudo-hypertrophy. | calpain 3 | C2C12 (mouse myoblast) cells. L6 (rat myoblast) cells. H9c2 (rat cardiomyoblast) cells. SK-MES-1 (human lung squamous cell carcinoma) cells. | |||
| 112 | Cardiac arrhythmia, ankyrin-b-related | ANK2 | Certain loss-of-function ANK2 variants are associated with a primarily cardiac-presenting autosomal-dominant condition with incomplete penetrance and variable expressivity characterized by a predisposition to supraventricular and ventricular arrhythmias, arrhythmogenic cardiomyopathy, congenital and adult-onset structural heart disease, and sudden death. Another independent group of ANK2 variants are associated with increased risk for distinct neurological phenotypes, including epilepsy and autism spectrum disorders. | ankyrin 2 | HEK293 (human embryonic kidney) cells. COS-7 (African green monkey kidney) cells. H9c2 (rat cardiomyoblast) cells. Neuro2a (mouse neuroblastoma) cells. SH-SY5Y (human neuroblastoma) cells. | |||
| 113 | Cardiospondylocarpofacial syndrome | MAP3K7 | Cardiospondylocarpofacial syndrome (CSCF) is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion, extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations | mitogen-activated protein kinase kinase kinase 7 | HeLa cells: Cervical cancer cells HEK293 cells: Human embryonic kidney cells A549 cells: Human lung carcinoma cells MCF-7 cells: Breast cancer cell line Rat primary hepatocytes: Liver cells Rat cardiomyocytes: Heart muscle cells Rat fibroblasts PC12 cells: Rat pheochromocytoma cells | |||
| 114 | Caroli disease | PKHD1 | Caroli disease is a rare, congenital condition characterized by segmental dilation of large, intrahepatic bile ducts, which appear as cysts on imaging studies and histopathological examination. This condition is included in a group of congenital disorders known as fibropolycystic liver diseases, which originate from ductal plate malformations during embryological development. Patients with Caroli disease may frequently experience complications such as hepatolithiasis and recurrent cholangitis. Additionally, the patients are at increased risk for cholangiocarcinoma due to bile stasis and chronic inflammation. | PKHD1 ciliary IPT domain containing fibrocystin/polyductin | MDCK (Madin-Darby Canine Kidney) cells. HEK293 (human embryonic kidney) cells. HepG2 (human liver carcinoma) cells. HK-2 (human kidney proximal tubule) cells. | |||
| 115 | Carvajal syndrome | CTDSPL | Carvajal syndrome is characterized by woolly hair, striate palmoplantar keratoderma and left-sided ventricular cardiomyopathy leading to sudden cardiac death. It is inherited as autosomal recessive disorder due to defect in desmoplakin gene.[1] Early recognition of the condition through cutaneous arkers can lead to early intervention thereby reducing morbidity and mortality. | desmoplakin | HEK293 (human embryonic kidney) cells. U2OS (human osteosarcoma) cells. MCF-7 (human breast cancer) cells. HCT116 (human colorectal cancer) cells. | |||
| 116 | CDKL5-deficiency disorder | CDKL5 | CDKL5 deficiency disorder is characterized by seizures that begin in infancy, followed by significant delays in many aspects of development. Seizures in CDKL5 deficiency disorder usually begin within the first 3 months of life, and can appear as early as the first week after birth. | cyclin dependent kinase like 5 | SH-SY5Y cells: Human neuroblastoma HEK293 cells- Human embryonic kidney cell iPSC-derived neurons: Induced pluripotent stem cells (iPSCs) U87 glioblastoma cells: Human glioblastoma cells Rat primary cortical neuron PC12 cells: This rat pheochromocytoma cell line Rat hippocampal neurons: Rat astrocytes: Glial cells | |||
| 117 | Central core disease | RYR1 | Central core disease is a disorder that affects muscles used for movement (skeletal muscles). This condition causes muscle weakness that ranges from barely noticeable to very severe. The severity of muscle weakness may differ even among affected members of the same family. | ryanodine receptor 1 | C2C12 (mouse myoblast) cells. L6 (rat myoblast) cells. H9c2 (rat cardiomyoblast) cells. RD (human rhabdomyosarcoma) cells. SK-MES-1 (human lung squamous cell carcinoma) cells. | |||
| 118 | Cerebrofaciothoracic dysplasia | TMCO1 | Cerebro-facio-thoracic dysplasia is a rare condition characterized by abnormal development (dysplasia) of the brain (cerebro) and structures in the face (facio) and torso (thoracic). The problems with development lead to the key features of cerebro-facio-thoracic dysplasia, which include severe intellectual disability, distinctive facial features, and abnormalities of the ribs and spinal bones | transmembrane and coiled-coil domains 1 | SH-SY5Y (human neuroblastoma) cells. MCF-7 (human breast cancer) cells. HEK293 (human embryonic kidney) cells. | |||
| 119 | Charcot-Marie-Tooth disease type 1A | PMP22 | Charcot-Marie-Tooth disease type 1A (CMT1A) is a type of inherited neurological disorder that affects the peripheral nerves. People with this disease experience weakness and wasting (atrophy) of the muscles of the lower legs beginning in adolescence; later they can also have hand weakness and sensory loss. CMT1A is caused by having an extra copy (a duplication) of the PMP22 gene. It is inherited in an autosomal dominant manner. | peripheral myelin protein 22 | Schwann cells HEK293 cells- human embryonic kidney cell iPSC-derived Schwann cells: Induced pluripotent stem cells (iPSCs) Rat Schwann cells: Similar to humans, Rat dorsal root ganglion (DRG) neurons: These neurons, along with their supporting Schwann cells, PC12 cells: Rat pheochromocytoma cells | |||
| 120 | Charcot-Marie-Tooth disease type 1E | PMP22 | A rare subtype of CMT1 characterized by a variable clinical presentation. Onset within the first two years of life with a delay in walking is not uncommon; however, onset may occur later. CMT1E is caused by point mutations in the PMP22 (17p12) gene. The disease severity depends on the particular PMP22 mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients | peripheral myelin protein 22 | Schwann cells HEK293 cells- human embryonic kidney cell iPSC-derived Schwann cells: Induced pluripotent stem cells (iPSCs) Rat Schwann cells: Similar to humans, Rat dorsal root ganglion (DRG) neurons: These neurons, along with their supporting Schwann cells, PC12 cells: Rat pheochromocytoma cells | |||
| 121 | Charcot-Marie-Tooth disease type 4B2 | SBF2 | Charcot-Marie-Tooth disease type 4B2 (CMT4B2) is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves can result in loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands. CMT4B2 can also cause glaucoma (damage to the eye's optic nerve). CMT4B2 is inherited in an autosomal recessive fashion. It is caused by genetic changes in the SBF1 gene. | SET binding factor 2 | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells iPSC-derived Schwann cells: Induced pluripotent stem cells U87 glioblastoma cells: These human brain cancer cells Rat Schwann cells PC12 cells: This rat pheochromocytoma cell line Rat dorsal root ganglion (DRG) neurons: In conjunction with Schwann cell | |||
| 122 | Cherubism | SH3BP2 | Cherubism is a childhood-onset, autoinflammatory bone disease characterized by bilateral and symmetric proliferative fibroosseous lesions limited to the mandible and maxilla. The enlargement is usually symmetric in nature. The phenotype ranges from no clinical manifestations to severe mandibular and maxillary overgrowth with respiratory, vision, speech, and swallowing problems. In most affected persons, teeth are displaced, unerupted, unformed, or absent, or may appear to be floating in cystlike spaces; malocclusion, premature exfoliation of deciduous teeth, and root resorption have also been reported. The course and duration of the active process of bone destruction varies between affected individuals; the onset is usually in early childhood, and typically new lesions can occur until puberty. | SH3 domain binding protein 2 | HeLa cells: Human cervical cancer cells HEK293 cells: These human embryonic kidney cells THP-1 cells: A human monocytic cell line U937 cells: Another human immune cell line Rat macrophages cells PC12 cells: Rat pheochromocytoma cells Rat osteoblasts: bone-forming cells | |||
| 123 | Childhood encephalopathy due to thiamine pyrophosphokinase deficiency | TPK1 | Thiamine metabolism dysfunction syndrome-5 (THMD5) is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. | thiamin pyrophosphokinase 1 | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells MCF-7 cells: Human breast cancer cells HepG2 cells: Human liver carcinoma cells Rat hepatocytes: Primary liver cells Rat fibroblasts PC12 cells: Rat pheochromocytoma cells Rat cardiomyocytes: Heart muscle cells | |||
| 124 | Choroid plexus carcinoma | TP53 | Choroid plexus carcinoma is a rare type of brain cancer that happens mainly in children. Choroid plexus carcinoma begins as a growth of cells in the part of the brain called the choroid plexus. Cells in the choroid plexus produce the fluid that surrounds and protects the brain and spinal cord. This fluid is called cerebrospinal fluid, also known as CSF. As the cancer grows, it can cause too much CSF in the brain. This can lead to symptoms such as irritability, nausea or vomiting, and headaches. | tumor protein p53 | HeLa cells: Human cervical cancer cells HEK293 cells: These human embryonic kidney cells MCF-7 cells: Breast cancer cells HCT116 cells: Human colon cancer cells Rat hepatocytes: Primary liver cells Rat cardiomyocytes: Heart muscle cells PC12 cells: Rat pheochromocytoma cells | |||
| 125 | Choroideremia | 1 in 50,000 to 1 in 100,000 people worldwide. | CHM | REP-1: Rab Escort Protein 1, TCD, Rab Proteins Geranylgeranyltransferase Component A 1 | Choroideremia is a rare genetic disorder characterized by progressive vision loss due to the degeneration of the choroid,retinal pigment epithelium (RPE), and photoreceptors in the eye.It primarily affects males, while females are usually carriers with milder symptoms due to its X-linked recessive inheritance pattern. | CHM Rab escort protein | ||
| 126 | Chudley-McCullough syndrome | less than 1 in 1 million | GPSM2 | LGN , Pins, G-Protein Signalling Modulator 2 (AGS3-Like, C. Elegans), G-Protein-Signaling Modulator 2 , Mosaic Protein LGN DFNB82 Deafness, Autosomal Recessive 82 CMCS 3 | Chudley-McCullough syndrome (CMCS) is a rare autosomal recessive genetic disorder that manifests with congenital hearing loss and a variety of brain malformations. It is caused by mutations GPSM2 (G-protein signaling modulator 2) gene, and characterized bya typical combination of brain malformations, including ventriculomegaly, (partial)agenesis of the corpus callosum, cerebellar dysplasia, arachnoid cysts, frontal subcortical heterotopia, and midline polymicrogyria | G protein signaling modulator 2 | HeLa cells: Human cervical cancer HEK293 cells: Human embryonic kidney cells U2OS cells: Human osteosarcoma cells MCF-7 cells: Breast cancer cells Rat primary neurons PC12 cells: Rat pheochromocytoma cells Rat fibroblasts | |
| 127 | Chédiak-Higashi syndrome | about 1 in 1,000,000 to 1 in 1,500,000 live births worldwide | LYST | CHS, Mauve CHS1, Lysosomal trafficking regulator Beige homologue | Chediak Higashi syndrome (CHS) is an autosomal recessive disorder that is characterized by easy bruising,oculocutaneous albinism and recurrent pyogenic infections. The defect is caused by a mutation in the lysosomal trafficking regulator protein that leads todecreased phagocytosis and predisposition to recurrent bacterial infection. | G Lysosomal trafficking regulator gene | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells THP-1 cells: A human monocytic cell line U937 cells: human immune cell line Rat primary macrophages Rat fibroblasts PC12 cells: Rat pheochromocytoma cells e Rat primary neurons | |
| 128 | Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome | less than 1 in 1,000,000 | SLC30A10 | ZNT10, Solute carrier family 30 member 10, ZRC1 Calcium/Manganese Antiporter SLC30A10 , Zinc Transporter 10 Zinc Transporter 8 DKFZp547M236 Zinc Resistance Conferring Homolog Manganese Transporter SLC30A10 HMNDYT1 HMDPC | Hypermanganesaemia with dystonia, polycythemia, and cirrhosis (HMDPC) is a rare genetic and autosomal recessive disorder that occurs due to mutation of the SLC3A10 gene, which encodes the manganese (Mn) transporter in the body; as a result, Mn accumulates in the brain, liver and muscles. This accumulation leads to symptoms of generalized dystonia, polycythemia, and hypermanganesaemia. | Solute carrier family 30 member 10 | ||
| 129 | Classic galactosemia | GALT | Classic galactosemia, which can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage, bleeding, and E coli sepsis in untreated infants. If a lactose-restricted diet is provided during the first ten days of life, the neonatal signs usually quickly resolve and the complications of liver failure, sepsis, and neonatal death are prevented; however, despite adequate treatment from an early age, children with classic galactosemia remain at increased risk for developmental delays, speech problems (termed childhood apraxia of speech and dysarthria), and abnormalities of motor function. Almost all females with classic galactosemia manifest hypergonadatropic hypogonadism or premature ovarian insufficiency (POI). | galactose-1-phosphate uridylyltransferase | ||||
| 130 | Classic glucose transporter type 1 deficiency syndrome | 1 in 90,000 livebirths worldwide | SLC2A1 | GLUT1 (Glucose Transporter Type 1) Dystonia 9 (DYT9), Solute carrier family 2, facilitated glucose transporter member 1 | Glucose Transporter Type 1 Deficiency Syndrome (GLUT1DS), also known as De Vivo disease, is a rare genetic disorder that affects the brain's ability to effectively utilize glucose, the primary source of energy. This condition is caused by mutations in the SLC2A1 gene, which encodes the glucose transporter protein GLUT1. The classic GLUT1-DS manifestations include infantile seizures, acquired microcephaly, developmental delay, hypotonia, and a complex movement disorder including elements of dystonia, spasticity, and ataxia. | Solute carrier family 2, facilitated glucose transporter member 12 | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells a MCF-7 cells: Breast cancer cells HepG2 cells: Human liver carcinoma cells Rat primary neurons PC12 cells: Rat pheochromocytoma cell Rat hepatocytes: Liver cells Rat cardiac myocytes: Heart muscle cells | |
| 131 | Classic hairy cell leukemia | 0.3 Cases in 100,000 people | BRAF | BRAF proto-oncogene, serine/threonine kinase, v-Raf murine sarcoma viral oncogene homolog B1, BRAF1 | Hairy Cell Leukemia (HCL) is a rare, indolent B-cell neoplasm. It is characterized by the progressive infiltration by mature lymphocytes with typical “hairy” projections within the peripheral blood (PB), bone marrow (BM) and spleen,resulting in pancytopenia, splenomegaly, and susceptibility to infections . A characteristic molecular feature of the disease, present in ≥95% of cases, is the BRAFV600E somatic mutation. It is important to distinguish between classic HCL and HCL-like diseases, including splenic B-cell lymphoma/leukemia, unclassifiable, as well as the variant form of HCL (HCL-v) and the splenic diffuse red pulp lymphoma (SDRPL). Monocytopenia is characteristic of classic HCL . | B-raf proto-oncogene, serine/threonine kinase | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells A375 cells: A human melanoma cell line HCT116 cells: Human colon cancer cells Rat primary neurons Rat hepatocytes: Liver cells PC12 cells: Rat pheochromocytoma cells Rat fibroblasts | |
| 132 | Cleidocranial dysplasia | 1 in 1,000,000 individuals | RUNX2 | CBFA1 (Core-binding factor subunit alpha-1) AML3 (Acute myeloid leukemia 3) PEBP2A1 (Polyomavirus enhancer-binding protein 2 alpha A subunit) OSF2 (Osteoblast-specific transcription factor 2) | Cleidocranial dysplasia (CCD) is a rare autosomal dominant condition with generalized dysplasia of bone characterized by delayed closure of cranial sutures, hypoplastic or aplastic clavicles , short stature, dental abnormalities and a variety of other skeletal abnormalities. The condition is caused by mutations in the RUNX2 gene, which is crucial for osteoblast differentiation and skeletal morphogenesis. The most common symptoms of cleidocranial dysplasia include: Delayed closing of the soft spots on the skull (fontanelles) and connecting joints of the skull (sutures).Underdeveloped or missing collarbones (clavicles). Permanent teeth emerging late, failure to lose primary teeth, extra teeth and dental crowding and abnormal alignment of the teeth (malocclusion). | RUNX family transcription factor 2 | MC3T3-E1 cells: A mouse osteoblast cell line MG63 cells: A human osteosarcoma cell line SaOS-2 cells: Human osteosarcoma cells U2OS cells: Human osteosarcoma cells Rat primary osteoblasts: Cells derived from rat bone Rat calvarial osteoblasts: Osteoblasts isolated from rat skull bones Rat bone marrow stromal cells | |
| 133 | CLN10 disease | Prevalence is 1.2/1,000,000 | CTSD | Cathepsin D CLN10 CPSD MGC2311 | CLN10 disease, also known as congenital neuronal ceroid lipofuscinosis or cathepsin D deficiency, is a rare and severe form of neuronal ceroid lipofuscinosis (NCL). NCLs are a group of progressive neurodegenerative lysosomal storage disorders characterized by the accumulation of lipofuscin-like substances in various tissues, including the brain. CLN10 disease is caused by mutations in the CTSD gene, which encodes the enzyme cathepsin | Cathepsin D | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells U937 cells: Human monocytic cells HepG2 cells: Human liver carcinoma cells Rat primary hepatocytes: Liver cells f Rat cardiomyocytes: Heart muscle cells PC12 cells: Rat pheochromocytoma cells | |
| 134 | COG6-CGD | 1/200,000 and 1/250,000 live | COG6 | Component of Oligomeric Golgi Complex 6 | COG6 (Component of Oligomeric Golgi Complex 6) is associated with a specific type of Congenital Disorders of Glycosylation (CDG), known as CDG-II or CDG syndrome type II. CDG-II is a group of genetic disorders characterized by defects in glycosylation, a process crucial for attaching sugar molecules to proteins and lipids.In CDG-II related to COG6 mutations, the impairment typically affects the functioning of the Golgi apparatus, a cellular organelle responsible for modifying, sorting, and packaging proteins and lipids. As a component of the COG complex (a multi-subunit protein complex), COG6 plays a vital role in maintaining the structure and function of the Golgi apparatus. Mutations in the COG6 gene disrupt the assembly or stability of the COG complex, leading to abnormalities in glycosylation processes. | Component of oligomeric Golgi complex 6 | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells U2OS cells: Human osteosarcoma cells MCF-7 cells: Human breast cancer cells Rat primary neurons Rat fibroblasts PC12 cells: Rat pheochromocytoma cells | |
| 135 | Cohen syndrome | 1 in 100,000 to 1 in 250,000 individuals worldwide | VPS13B | COH1, Chorein, Vacuolar protein sorting-associated protein 13B, ChAc1 | Cohen syndrome is a rare genetic disorder characterized by distinct facial features, intellectual disability, developmental delays, joint hypermobility, progressive vision problems, and possible neutropenia. It is caused by mutations in the VPS13B gene and is inherited in an autosomal recessive manner. Management involves supportive care to address symptoms such as educational support, physical therapy, and vision care. | vacuolar Protein sorting 13 homolog. | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells Jurkat cells: A human T-cell leukemia line U937 cells: Human monocytic cells Rat primary macrophage Rat fibroblasts PC12 cells: Rat pheochromocytoma cells | |
| 136 | Combined immunodeficiency due to DOCK8 deficiency | DOCK8 | CID due to DOCK8 deficiency is caused by homozygous or compound heterozygous deletions and point mutations in the DOCK8 gene (9p24), which leads to an absence of DOCK8 protein in lymphocytes, resulting in low absolute T and B lymphocyte counts, mild-to-moderate eosinophilia and very high levels of serum IgE. | dedicator of cytokinesis 8 | ||||
| 137 | Combined immunodeficiency due to STIM1 deficiency | STIM1 | CID due to STIM1 deficiency is characterized by recurrent viral, bacterial, mycobacterial and fungal infections from birth, chronic diarrhea, pneumonia, meningitis, enteritis, gastrointestinal candidiasis, sepsis and otitis media. In addition, patients present at birth with congenital myopathy (see this term), characterized by non-progressive generalized muscular dysplasia. This presents as global muscular hypotonia and partial iris hypoplasia. All patients present with ectodermal dysplasia that is characterized by hypocalcified amelogenesis imperfecta (see this term) and leads to the loss of soft dental enamel. . | stromal interaction molecule 1 | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells Jurkat cells: A human T-cell leukemia line U2OS cells: Human osteosarcoma cells Rat primary neurons Rat cardiac myocytes: Heart muscle cells Rat fibroblasts: Fibroblast cells PC12 cells: Rat pheochromocytoma cells | |||
| 138 | Combined immunodeficiency due to ZAP70 deficiency | ZAP70 | AP70-related combined immunodeficiency (ZAP70-related CID) is a cell-mediated immunodeficiency caused by abnormal T-cell receptor (TCR) signaling. Affected children usually present in the first year of life with recurrent bacterial, viral, and opportunistic infections, diarrhea, and failure to thrive. Severe lower-respiratory infections and oral candidiasis are common. Affected children usually do not survive past their second year without hematopoietic stem cell transplantation (HSCT). | zeta chain of T-cell receptor associated protein kinase 70 | Jurkat cells: A human T-cell leukemia line Raji cells: A human B-cell line HeLa cells: While not a T-cell line, HeLa cells can be used H9 cells: A human T-cell line Rat primary T-cells Rat thymocytes: Immature T-cells PC12 cells: Rat pheochromocytoma cells | |||
| 139 | Cone-rod dystrophy 6 | GUCY2D | Cone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss | guanylate cyclase 2D, retinal | ||||
| 140 | Cone-rod dystrophy, x-linked, 1 | RPGR | X-linked cone dystrophy is a type of hereditary retinal degeneration characterized by a progressive dysfunction of the day vision or photopic (cone) system with preservation of night vision or scotopic (rod) function. The disease presents with a triad of photophobia, loss of color vision and reduced central vision. This phenotype is distinct from retinitis pigmentosa (RP) in which there are prominent night and peripheral vision disturbances. | retinitis pigmentosa GTPase regulator | ARPE-19 cells: A human retinal pigment epithelial cell line RPE65 cells: Though primarily used for studies on retinal disease models, HeLa cells: Human cervical cancer cells Rat primary retinal cells Rat retinal pigment epithelium (RPE) cells PC12 cells: Rat pheochromocytoma cells | |||
| 141 | Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency | CYP11B1 | Congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency is one of a group of disorders (collectively called congenital adrenal hyperplasia) that affect the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with CAH due to 11-beta-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones. | cytochrome P450 family 11 subfamily B member 1 | H295R cells: A human adrenal cortical carcinoma cell line H9c2 cells: Human embryonic heart cells Rat adrenal cortex cells: Primary cells from the rat adrenal gland PC12 cells: Though primarily a neuronal cell line | |||
| 142 | Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency | POR | A rare form of congenital adrenal hyperplasia due to P450 oxidoreductase deficiency and characterized by glucocorticoid deficiency, virilization of external genitalia in females, and undervirilization in males. Findings range from severely affected infants with 46,XX and 46,XY disorders/differences of sex development (DSD) and cortisol deficiency to mildly affected women who appear to have polycystic ovary syndrome, or mildly affected men with gonadal insufficiency. | cytochrome p450 oxidoreductase | H295R cells: A human adrenal cortical carcinoma cell line H9c2 cells: Human embryonic heart cells Rat adrenal cortex cells: Primary cells from the rat adrenal gland PC12 cells: Though primarily a neuronal cell line | |||
| 143 | Congenital dyserythropoietic anemia type III | KIF23 | Congenital dyserythropoietic anemia (CDA) is a group of rare hereditary disorders with ineffective erythropoiesis and distinct dyserythropoietic changes in the bone marrow. Three major types (I, II, and III) and several subtypes have been described.1-3 CDA III is the rarest form of the 3 classical CDAs, with about 60 cases described globally, the majority belonging to a family in Sweden. The disease is characterized by intravascular hemolysis in combination with dyserythropoiesis with large multinucleated erythroblasts (gigantoblasts) in the bone marrow. | kinesin family member 23 | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells U2OS cells: Human osteosarcoma cells HCT116 cells: Human colon cancer cells Rat primary fibroblasts Rat cardiomyocytes: Heart muscle cells PC12 cells: Rat pheochromocytoma cells | |||
| 144 | Congenital factor II deficienc | F2 | Congenital FII deficiency can manifest at any age, with severe forms of the disease manifesting early in life. Common clinical signs include epistaxis, menorrhagia, oral cavity bleedings, mucosal bleeding, soft tissue bleeding, hemarthrosis, easy bruising, and prolonged bleeding after tooth extraction, trauma or surgery. Severe forms may present intracranial hemorrhage. The severity of the bleeding manifestations correlates with the FII levels. Thromboembolic manifestations have been described in case of dysprothrombinemia | coagulation factor II, thrombin | HepG2 cells: Human liver carcinoma cells Hela cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells Rat primary hepatocytes: Liver cells Rat liver cell lines: Such as the BRL 3A cell line | |||
| 145 | Congenital factor V deficiency | F5 | Factor V deficiency is a rare bleeding disorder that can be inherited or acquired. Factor V is a vital component of the coagulation cascade, a glycoprotein synthesized primarily in the liver and released in the bloodstream in an inactive form. Blood vessel injury activates blood clotting factors, including factor V. Activated factor V ultimately accelerates fibrinogen conversion to fibrin, the protein meshwork that reinforces the clot. | coagulation factor V | HepG2 cells: Human liver carcinoma cells HEK293 cells: Human embryonic kidney cells Hela cells: Human cervical cancer cells Rat primary hepatocytes: Liver cells Rat liver cell lines: Such as the BRL 3A cell line | |||
| 146 | Congenital factor VII deficiency | F7 | Clinical expression of this disorder is highly variable and no consistent relationship has been found between the severity of the hemorrhagic syndrome and the residual levels of FVII activity. The clinical picture can be very severe, with early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, may be moderate with cutaneous/mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by surgery or trauma. Finally, numerous subjects are completely asymptomatic despite a very low FVII level. | coagulation factor VII | HepG2 cells: Human liver carcinoma cells HEK293 cells: Human embryonic kidney cells Hela cells: Human cervical cancer cells Rat primary hepatocytes: Liver cells Rat liver cell lines: Such as BRL 3A cells | |||
| 147 | Congenital factor X deficiency | F10 | Factor X deficiency is a rare bleeding disorder that varies in severity among affected individuals. The signs and symptoms of this condition can begin at any age, although the most severe cases are apparent in childhood. Factor X deficiency commonly causes nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, blood in the urine (hematuria), and prolonged or excessive bleeding following surgery or trauma. | coagulation factor X | HepG2 cells: Human liver carcinoma cells HEK293 cells: Human embryonic kidney cells Hela cells: Human cervical cancer cells Rat primary hepatocytes: Liver cells Rat liver cell lines: Such as BRL 3A cells | |||
| 147 | Congenital factor VII deficiency | F7 | Clinical expression of this disorder is highly variable and no consistent relationship has been found between the severity of the hemorrhagic syndrome and the residual levels of FVII activity. The clinical picture can be very severe, with early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, may be moderate with cutaneous/mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by surgery or trauma. Finally, numerous subjects are completely asymptomatic despite a very low FVII level. | coagulation factor VII | HepG2 cells: Human liver carcinoma cells HEK293 cells: Human embryonic kidney cells Hela cells: Human cervical cancer cells Rat primary hepatocytes: Liver cells Rat liver cell lines: Such as BRL 3A cells | |||
| 148 | Congenital factor XI deficiency | F11 | Factor XI deficiency is a rare genetic bleeding disorder caused by reduced levels and insufficient activity of a blood protein called factor XI. Factor XI is a clotting factor. Clotting factors are specialized proteins that are essential for proper clotting, the process by which blood solidifies like glue to plug the site of a wound to stop bleeding. Individuals with factor XI deficiency do not bleed faster or more profusely than healthy individuals, but, because their blood clots poorly, they may have difficulty stopping the flow of blood from a deep or surgical wound. | coagulation factor XI | ||||
| 149 | Congenital hereditary endothelial dystrophy type II | SLC4A11 | Congenital hereditary endothelial dystrophy (CHED) presents as bilateral corneal opacification present at birth or in the immediate newborn period and is due to an autosomal recessive mutation affecting the corneal endothelium.[1][2] Opacification is the result of stromal edema and Descemet membrane thickening due to endothelial dysfunction | solute carrier family 4 member 11 | ||||
| 150 | Congenital intrinsic factor deficiency | CBLIF | Congenital intrinsic factor deficiency is a rare condition that is characterized by pernicious anemia and neurological abnormalities. Symptoms may include failure to thrive and symptoms related to anemia (i.e. fatigue, pale skin, etc.). Nervous system damage may occur which can be associated with confusion; depression; and numbness or tingling in the hands and/or feet. Congenital intrinsic factor deficiency is caused by changes in the GIF gene and is inherited in an autosomal recessive manner. | cobalamin binding intrinsic factor | HeLa cells: Human cervical cancer cells HEK293 cells: Human embryonic kidney cells CFTR-expressing cell lines: human bronchial epithelial cell line Rat primary neurons Rat fibroblasts | |||
| 151 | Congenital multicore myopathy with external ophthalmoplegia | RYR1 | Congenital myopathy-1B (CMYO1B) is an autosomal recessive disorder of skeletal muscle characterized by severe hypotonia and generalized muscle weakness apparent soon after birth or in early childhood with delayed motor development, generalized muscle weakness and atrophy, and difficulty walking or running. Affected individuals show proximal muscle weakness with axial and shoulder girdle involvement, external ophthalmoplegia, and bulbar weakness, often resulting in feeding difficulties and respiratory insufficiency. Orthopedic complications such as joint laxity, distal contractures, hip dislocation, cleft palate, and scoliosis are commonly observed. Serum creatine kinase is normal. | ryanodine receptor 1 | ||||
| 152 | Congenital muscular dystrophy, Fukuyama type | FKTN | Fukuyama congenital muscular dystrophy (FCMD) is characterized by dystrophic changes in the skeletal muscle and by CNS migration disturbances resulting in cerebral and cerebellar cortical dysplasia. The clinical features are hypotonia, weakness, and psychomotor retardation. Mild, typical, and severe phenotypes are recognized. The phenotypic spectrum ranges from a Walker-Warburg syndrome (WWS)-like phenotype at the severe end to a limb-girdle muscular dystrophy-like phenotype at the mild end | fukutin | HEK293 cells: Human embryonic kidney cells C2C12 cells: A human myoblast cell line Hela cells: Human cervical cancer cells Rat primary myoblasts: These muscle precursor cells Rat skeletal muscle cells | |||
| 153 | Congenital nephrotic syndrome, Finnish type | NPHS1 | Congenital nephrotic syndrome Finnish type is a genetic condition of the kidney that begins early in development during pregnancy or within the first three months of life. The syndrome is characterized by a group of symptoms, including protein in the urine (proteinuria), low blood protein levels, high cholesterol levels, and swelling (nephrotic syndrome), which progresses rapidly to end-stage kidney disease. Infants with congenital nephrotic syndrome may have failure to thrive and frequent infections. Although more commonly seen in individuals of Finnish descent, Congenital nephrotic syndrome Finnish type has been reported worldwide. Congenital nephrotic syndrome Finnish type is caused by genetic changes in the NPHS1 gene and is inherited in an autosomal recessive manner | NPHS1 adhesion molecule, nephrinn | ||||
| 154 | Congenital sucrase-isomaltase deficiency | SI | Congenital sucrase-isomaltase deficiency is a rare genetic disorder that affects an individual's ability to digest certain sugars. People with this condition cannot break down the sugars sucrose and maltose. Sucrose (a sugar found in fruits, and also known as table sugar) and maltose (the sugar found in grains) are called disaccharides because they are made of two simple sugars. Disaccharides are broken down into simple sugars during digestion. Sucrose is broken down into glucose and another simple sugar called fructose, and maltose is broken down into two glucose molecules. People with congenital sucrase-isomaltase deficiency cannot break down the sugars sucrose and maltose, and other compounds made from these sugar molecules (carbohydrates). | sucrase-isomaltase | Caco-2 cells: A human colorectal cancer cell line HT29 cells: Human colorectal cancer cells Intestinal epithelial cell lines: Such as T84 cells Rat primary enterocytes Rat intestinal cell lines | |||
| 155 | Congenital thrombotic thrombocytopenic purpura | About 1 in 1,000,000 worldwide | ADAMTS13 | VWF-CP C9orf8 VWFCP A Disintegrin-Like And Metalloprotease (Reprolysin Type) With Thrombospondin Type 1 Motif, A Disintegrin And Metalloproteinase With Thrombospondin Motifs Von Willebrand Factor-Cleaving Protease VWF-Cleaving Protease DKFZp434C2322 MGC118899 MGC118900 ADAM-TS13 ADAMTS-13 FLJ42993 TTP | Congenital thrombotic thrombocytopenic purpura (congenital TTP) is a blood disorder in which blood clots form in the small blood vessels throughout the body. Symptoms typically develop in infancy or early childhood, but in some cases they do not develop until adulthood. Symptoms generally are due to hemolytic anemia, low platelets (thrombocytopenia), and neurologic dysfunction. Symptoms of anemia can include fatigue, paleness, jaundice, shortness of breath, and a rapid heart rate. Widespread thrombosis (abnormal clotting) can lead to problems with the nervous system (such as personality changes, headaches, confusion, and seizures), abnormal kidney function, heart problems, and gastrointestinal problems. Congenital TTP is caused by changes in the ADAMTS13 gene and inheritance is autosomal recessive. | ADAM metallopeptidase with thrombospondin type 1 motif 13 | CHO - Chinese hamster ovary cells, often used in recombinant protein expression. COS-7 - A fibroblast-like cell line derived from monkey kidney tissue. HEK293 - Human embryonic kidney cells. | |
| 156 | Corneal dystrophy-perceptive deafness syndrome | Unknown | SLC4A11 | NaBC1 BTR1 DJ794I6.2 Solute Carrier Family 4, Sodium Bicarbonate Transporter-Like, Member 11 Solute Carrier Family 4, Sodium Borate Transporter, Member 11 Bicarbonate Transporter Related Protein 1 Sodium-Coupled Borate Cotransporter 1 FECD4 CDPD1 CHED2 Corneal Endothelial Dystrophy 2 (Autosomal Recessive) Corneal Dystrophy And Perceptive Deafness Sodium Borate Cotransporter CHED | corneal dystrophy and perceptive deafness syndrome, also known as Harboyan syndrome or Harboyan syndrome with corneal dystrophy and perceptive deafness, is an extremely rare genetic disorder characterized by corneal dystrophy (specifically, lattice corneal dystrophy type 2) and sensorineural hearing loss.Harboyan syndrome is inherited in an autosomal recessive manner, meaning individuals must inherit two copies of the mutated gene (one from each parent) to develop the condition. The specific genetic mutation responsible for Harboyan syndrome has been identified. SLC4A11 encodes a membrane transporter protein that is crucial for maintaining corneal transparency and regulating fluid and ion transport across the corneal endothelium. Mutations in SLC4A11 can disrupt these functions, leading to the accumulation of abnormal deposits (amyloid) in the cornea, characteristic of lattice corneal dystrophy type 2. | solute carrier family 4 member 1 | ||
| 157 | Corpus callosum agenesis-neuronopathy syndrome | in approximately 1 in 4,000 live births. | SLC12A6 | K-Cl Cotransporter KCC3A KCC3B KCC3 Solute Carrier Family 12 (Potassium/Chloride Transporter), Member 6 Electroneutral Potassium-Chloride Cotransporter ACCPN Agenesis Of Corpus Callosum And Peripheral Neuropathy (Andermann Syndrome) 2 Solute Carrier Family 12 (Potassium/Chloride Transporters), Member 6 Potassium Chloride Cotransporter KCC3a-S3 Potassium Chloride Cotransporter Potassium-Chloride Transporter-3a Potassium-Chloride Transporter-3b | Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and neurodegenerative disorder, is characterized by severe progressive sensorimotor neuropathy with resulting hypotonia, areflexia, and amyotrophy, and by variable degrees of dysgenesis of the corpus callosum. Mild-to-severe intellectual disability and "psychotic episodes" during adolescence are observed. Sensory modalities are moderately to severely affected beginning in infancy. The average age of onset of walking is 3.8 years; the average age of loss of walking is 13.8 years; the average age of death is 33 years. | solute carrier family 12 member 6 | ||
| 158 | Curry-Jones syndrome | < 1 / 1 000 000 in worldwide | SMO | FZD11 SMOH Smoothened, Seven Transmembrane Spanning Receptor Smoothened, Frizzled Family Receptor Frizzled Family Member 11 Protein Smoothened Protein Gx Seven Transmembrane Helix Receptor Smoothened Homolog CRJS | Curry-Jones syndrome is a form of syndromic craniosynostosis characterized by unilateral coronal craniosynostosis or multiple suture synostosis associated with complete or partial agenesis of the corpus callosum, preaxial polysyndactyly and syndactyly of hands and/or feet, along with anomalies of the skin (characteristic pearly white areas that become scarred and atrophic, abnormal hair growth around the eyes and/or cheeks, and on the limbs), eyes (iris colobomas, microphthalmia,) and intestine (congenital short gut, malrotation, dysmotility, chronic constipation, bleeding and myofibromas). Developmental delay and variable degrees of intellectual disability may also be observed. Multiple intra-abdominal smooth muscle hamartomas, trichoblastoma of the skin, occipital meningoceles and development of desmoplastic medulloblastoma have been reported. | smoothened, frizzled class receptor | ||
| 159 | Cutaneous mastocytoma | KIT | Cutaneous mastocytoma is a form of cutaneous mastocytosis (CM, see this term) generally characterized by the presence of a solitary or multiple hyperpigmented macules, plaques or nodules associated with abnormal accumulation of mast cells in the skin. | KIT proto-oncogene, receptor tyrosine kinase | ||||
| 160 | Cyclic neutropenia | an estimated frequency of 1:1,000,000 in the general population worldwide | ELANE | HLE Neutrophil Elastase PMN Elastase Medullasin PMN-E ELA2 HNE NE Polymorphonuclear Leukocyte Elastase Bone Marrow Serine Protease Elastase 2, Neutrophil Leukocyte Elastase Elastase-2 Granulocyte-Derived Elastase Polymorphonuclear Elastase Human Leukocyte Elastase | Cyclic neutropenia is a very rare hematological condition characterized by regular fluctuations in blood neutrophil counts, leading to periodic neutropenia with a 21-day turnover frequency.It is now considered an autosomal dominant disease caused by ELANE gene mutations.The symptoms and clinical manifestation of cyclic neutropenia may range from mild to severe, depending on the degree and duration of neutropenia. The absolute neutrophil count can drop to zero, and these extremely low counts may last for up to three to five days. | elastase, neutrophil expressed | ||
| 161 | Deafness, autosomal dominant 22 | The incidence is ∼1 in 50,000 people, with the vast majority of cases inherited in an autosomal dominant fashion | MYO6 | KIAA0389 Unconventional Myosin-VI Unconventional Myosin-6 DFNA22 DFNB37 Deafness, Autosomal Recessive | Deafness, autosomal dominant 22 (DFNA22) is a type of hearing loss that is passed down in families. A gene called myosin VI (MYO6) on chromosome 6q14 is responsible for this condition. If you have a change in one copy of this gene, you may develop DFNA22.The main symptom is progressive sensorineural hearing loss, which is due to damage to the inner ear or the nerve pathways from the inner ear to the brain. The hearing loss in DFNA22 can vary in severity and progression.. | myosin VI | ||
| 162 | Denys-Drash syndrome | less than 1 in 100,000 live births | WT1 | GUD - Genitourinary Development NPHS4 - Nephrotic Syndrome Type 4 WAGR - Wilms Tumor, Aniridia, Genitourinary Anomalies, and Mental Retardation (referring to WAGR syndrome, which involves WT1 gene mutations) WT33 WIT-2 NPHS4 WAGR AWT1 | The Denys-Drash syndrome is characterised by the triad: progressive nephropathy due to diffuse mesangial sclerosis, male pseudo-hermaphroditism (XY karyotype with ambiguous or female genital organs) and an increased risk of developing Wilms' tumour and gonadoblastoma. The syndrome is generally caused by a genetic defect in the Wilms' tumour suppressor 1 gene (WT1 gene). A WT1 mutation and XY karyotype were also found in this patient . The WT1 gene encodes a transcription factor playing an important role in renal and genital development. | Wilms' tumour suppressor 1 gene | ||
| 163 | Dermatopathia pigmentosa reticularis | unknown | KRT14 | CK14 - Cytokeratin 14 K14 - Keratin 14 EBS3 - Epidermolysis Bullosa Simplex, Dowling-Meara Type EBS4 - Epidermolysis Bullosa Simplex, Koebner Type | Dermatopathia pigmentosa reticularis (DPR), a rare form of autosomal dominant ectodermal dysplasia.Defect in the N-terminal part of keratin molecule results in loss of inhibition against proapoptotic signals. KRT14 mutation has resulted in a case of dermatopathia pigmentosa reticularis with wiry scalp hair and digital fibromatosis.While reticulate hyperpigmentation involving the whole body, nail dystrophy, and nonscarring alopecia forms the classical triad of dermatopathia pigmentosa reticularis, other clinical features such as hypohidrosis or hyperhidrosis, palmoplantar thickening, and loss of dermatoglyphics and ainhum-like constrictions have also seen | keratin 14 | ||
| 164 | Desmosterolosis | < 1:10,000,000 is affected worldwide | DHCR24 | SELADIN1 - Selective Alzheimer Disease Indicator 1 C14orf1 - Chromosome 14 Open Reading Frame 1 (gene symbol) CH24H - Cholesterol 24-hydroxylase | Desmosterolosis is a rare multiple congenital anomaly syndrome caused by a defect in the enzyme 3-beta-hydroxysterol delta-24-reductase (DHCR24) in the cholesterol biosynthesis pathway. Defects in this enzyme cause increased level of the cholesterol precursor desmosterol while disrupting development of cholesterol, impacting embryogenesis. Signs and symptoms may include:Brain abnormalities Malformation of the tissue that connects the left and right halves of the brain (the corpus callosum), Loss of white matter, which consists of nerve fibers covered by a fatty substance called myelin Developmental delay | 24- dehydrocholesterol reductase | ||
| 165 | Developmental and epileptic encephalopathy 18 | SZT2 | KIAA0467 C1orf84 SZT2B SZT2A KICS1 Seizure Threshold 2 Protein Homolog | Developmental and Epileptic Encephalopathy 18, also known as epileptic encephalopathy, early infantile, 18, is related to developmental and epileptic encephalopathy 1 and early infantile epileptic encephalopathy, and has symptoms including absence seizures. An important gene associated with Developmental and Epileptic Encephalopathy 18 is SZT2 (SZT2 Subunit Of KICSTOR Complex). Affiliated tissues include brain, and related phenotypes are hypotonia and profound global developmental delay. | SZT2 subunit of KICSTOR complex | |||
| 166 | Developmental and epileptic encephalopathy 26 | KCNB1 | Kv2.1 - Potassium channel, voltage-gated, Shab-related subfamily, member 1 HBK1 - Human brain Kv channel 1 Kv2.1 Channel - Referring to the specific potassium channel subtype encoded by the KCNB1 gene SBC1 - Shab-related potassium channel 1 | Developmental and epileptic encephalopathy-26 (DEE26) is a neurologic disorder characterized by onset of variable types of seizures late in infancy or in the first years of life. Affected children show developmental delay with intellectual disability, poor speech, and behavioral abnormalities. EEG shows multifocal epileptic discharges, and may show hypsarrhythmia | potassium voltage-gated channel subfamily B member 1 | |||
| 167 | Developmental malformations-deafness-dystonia syndrome | ACTB | Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability. Many (but not all) affected individuals have pachygyria that is predominantly frontal, wasting of the shoulder girdle muscles, and sensory impairment due to iris or retinal coloboma and/or sensorineural deafness. Intellectual disability, which is common but variable, is related to the severity of the brain malformations. Seizures, congenital heart defects, renal malformations, and gastrointestinal dysfunction are also common. | potassium voltage-gated channel subfamily B member 1 | ||||
| 168 | Diaphyseal medullary stenosis-bone malignancy syndrome | MTAP | HMFN - Homo sapiens methylthioadenosine phosphorylase MTAPase - Methylthioadenosine phosphorylase MTA phosphorylase - Methylthioadenosine phosphorylase p16-accessory gene product | Diaphyseal medullary stenosis with malignant fibrous histiocytoma is an autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. In 2 families, affected individuals also showed a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma. Thus, the disorder may be considered a tumor predisposition syndrome | methylthioadenosine phosphorylase | |||
| 169 | Dihydropyrimidinuria | Fewer than 1,000 people in the U.S. have thi sdisease. | DPYS | DHPase Dihydropyrimidine Amidohydrolase Hydantoinase DHP | Dihydropyrimidinase (DPD) deficiency is a very rare pyrimidine metabolism disorder with a variable clinical presentation including gastrointestinal manifestations (feeding problems, cyclic vomiting, gastroesophageal reflux, malabsorption with villous atrophy), hypotonia, intellectual deficit, seizures, and less frequently growth retardation, failure to thrive, microcephaly and autism. DPD deficiency increases the risk of 5-FU toxicity. | dihydropyrimidinase | ||
| 170 | Distal renal tubular acidosis with anemia | SLC4A1 | An autosomal recessive disease characterized by the association of hemolytic anemia with distal renal tubular acidosis, the reduced ability to acidify urine resulting in variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. | solute carrier family 4 member 1 (Diego blood group) | ||||
| 171 | Distal renal tubular acidosis | prevalence of 0.46/10,000 inhabitants | WDR72 | AI1F (Amelogenesis Imperfecta 1F) WD40-repeat protein 72 | Distal RTA (dRTA), also called type 1 RTA, is a rare genetic disorder characterized by the inability of the distal nephron to maximally increase the urinary secretion of protons (H +) in the presence of metabolic acidosis.dRTA may develop symptoms very early, even during infancy, including failure to thrive, vomiting, polydipsia, polyuria, feeding problems, and episodes of dehydration .Mutations in the WDR72 gene typically follow an autosomal recessive inheritance pattern.Mutations in the WDR72 gene can disrupt normal kidney function, leading to the clinical manifestations of dRTA | WD repeat domain 72 | ||
| 172 | DOCK2 deficiency | DOCK2 | Dedicator of cytokinesis protein 2 HEF1-associated protein 2 (HEF1AP2) hsu12968 | DOCK2 deficiency is a rare primary immunodeficiency disorder caused by mutations in the DOCK2 gene, which encodes the dedicator of cytokinesis 2 protein. This protein plays a critical role in the regulation of the actin cytoskeleton, which is essential for the proper functioning of immune cells, particularly leukocytes. Patients with DOCK2 deficiency experience frequent and severe infections,ncluding bacterial, viral, and fungal infections, due to impaired immune cell function. | dedicator of cytokinesis 2 | |||
| 173 | Dopa-responsive dystonia due to sepiapterin reductase deficiency | SPR | Onset usually occurs before the first year of life with manifestations of dystonia, motor and language delays, weakness, axial hypotonia (and hypotonia in a tetraplegic distribution) and oculogyric crises that show diurnal fluctuations (worse at night and better in the morning after sleeping). Sleep disturbances and psychological symptoms (anxiety, irritability) are common later in childhood. Intellectual deficits are frequently noted but some may only experience mild to moderate learning disabilities. Less common features include parkinsonism (tremor, bradykinesia, rigidity, masked facies), dysarthria, hyperreflexia, limb hypertonia, and autonomic signs. Frequently, dystonia and obvious diurnal fluctuations only develop during the course of the disease, whereas common presenting symptoms in infancy such as developmental delay and hypotonia are unspecific. | sepiapterin reductase | ||||
| 174 | DPAGT1-CDG | DPAGT1 | DPAGT1-CDG is a form of congenital disorders of N-linked glycosylation characterized by hypotonia, intractable seizures, developmental delay, microcephaly and severe fetal hypokinesia. Additional features that may be observed include apnea and respiratory deficiency, cataracts, joint contractures, vermian hypoplasia, dysmorphic features (esotropia, arched palate, micrognathia, finger clinodactyly, single flexion creases) and feeding difficulties. The disease is caused by loss-of-function mutations in the gene DPAGT1 | dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 | ||||
| 175 | Dyskeratosis congenita, x-linked | ranges from 1 in 1 million to 1 in 100,000 individuals | DKC1 | CBF5, DKCB1, NAP57, NOLA4, XAP101 | X-linked Dyskeratosis Congenita (X-DC) is a rare inherited disorder primarily affecting males, caused by mutations in the DKC1 gene located on the X chromosome. This gene encodes the dyskerin protein, which plays a crucial role in maintaining telomere function and ribosome biogenesis. | dyskerin Pseudouridine syntase1 | ||
| 176 | Dyssegmental dysplasia, Silverman-Handmaker type | HSPG2 | Dyssegmental dysplasia, Silverman-Handmaker type is a rare, genetic, primary bone dysplasia disorder, and lethal form of neonatal short-limbed dwarfism, characterized by anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (i.e. flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (e.g. joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities. | heparan sulfate proteoglycan 2 | ||||
| 177 | Endosteal hyperostosis, Worth type | unknown | LRP5 | LRP5, BMND, BMND2, EVR1, HBM | Endosteal hyperostosis refers to excessive bone growth on the inner surface of bones. It can be associated with conditions like Diffuse Idiopathic Skeletal Hyperostosis (DISH), where there is abnormal calcification and ossification of ligaments and tendons near the spine and other areas of the body. This condition can lead to stiffness and pain in affected joints and may require medical management depending on its severity and impact on the individual's quality of life.The COL3A1 gene encodes for the pro-alpha1 chains of type III collagen, a protein that plays a crucial role in the structure and function of connective tissues, including those found in bones and cartilage. Mutations or alterations in COL3A1 can lead to various skeletal disorders, affecting bone strength and integrity. | LDL receptor related protein 5 | ||
| 178 | Endosteal hyperostosis, Worth type | unknown | LRP5 | LRP5, BMND, BMND2, EVR1, HBM | Endosteal hyperostosis refers to excessive bone growth on the inner surface of bones. It can be associated with conditions like Diffuse Idiopathic Skeletal Hyperostosis (DISH), where there is abnormal calcification and ossification of ligaments and tendons near the spine and other areas of the body. This condition can lead to stiffness and pain in affected joints and may require medical management depending on its severity and impact on the individual's quality of life.The COL3A1 gene encodes for the pro-alpha1 chains of type III collagen, a protein that plays a crucial role in the structure and function of connective tissues, including those found in bones and cartilage. Mutations or alterations in COL3A1 can lead to various skeletal disorders, affecting bone strength and integrity. | LDL receptor related protein 5 | ||
| 179 | Familial abdominal aortic aneurysm | 2.5 to 6.5 aneurysms per 1000 person-years | COL3A1 | COL3A1, EDSIV, EDSIII, PDS, ECTOL1 | A familial abdominal aortic aneurysm refers to the presence of abdominal aortic aneurysms (AAA) within a family, suggesting a genetic predisposition. AAAs are bulges in the wall of the abdominal aorta, potentially leading to serious complications if they rupture. A familial history increases the risk of developing an AAA, emphasizing the importance of screening and early detection in affected families. | Collagen type 3 alpha1 chain | ||
| 180 | Familial acute necrotizing encephalopathy | RANBP2 | Familial acute necrotizing encephalopathy or ADANE is a potentially fatal neurological disease characterised by neuropathological lesions principally involving the brainstem, thalamus and putamen.Onset occurs during early childhood, typically a few days after a febrile illness. Manifestations include vomiting, seizures, spasticity, language regression, rigidity and abnormal posturing of the head. Residual neurologic impairment (muscle weakness, speech disturbance, intellectual deficit and mood disorders) persists in some patients. The disease is chronic in one out of two cases. | RAN binding protein 2 | ||||
| 181 | Familial aortic dissection | MYH11 | Familial aortic dissection is the term used to describe rupture of the aortic wall at the level of the media, resulting in the formation of a false channel and deviation of part of the aortic flux. Familial predisposition to thoracic aortic aneurysms and type A dissections (concerning the ascending aorta and/or the aortic arch) has been demonstrated in around 19% of patients presenting with thoracic aortic dissections and several loci have been identified so far (16p12.2-p13.13, 3p24-25). This predisposition is transmitted in an autosomal dominant manner. | myosin heavy chain 11 | ||||
| 182 | Familial multiple nevi flammei | GNAQ | Familial multiple nevi flammei is a rare, genetic capillary malformation disorder characterized by dark red to purple birthmarks which manifest as flat, sharply circumscribed cutaneous lesions, typically situated in the head and neck region, in various members of a single family. The lesions grow proportionally with the individual, change in color and often thicken with age. | G protein subunit alpha q | ||||
| 183 | Familial paroxysmal ataxia | CACNA1A | A form of hereditary episodic ataxia (EA) characterized by paroxysmal episodes of ataxia lasting hours, with interictal nystagmus and mildly progressive ataxia. | alcium voltage-gated channel subunit alpha1 A | ||||
| 183 | Familial multiple nevi flammei | GNAQ | Familial multiple nevi flammei is a rare, genetic capillary malformation disorder characterized by dark red to purple birthmarks which manifest as flat, sharply circumscribed cutaneous lesions, typically situated in the head and neck region, in various members of a single family. The lesions grow proportionally with the individual, change in color and often thicken with age. | G protein subunit alpha q | ||||
| 184 | Fanconi-Bickel syndrome | SLC2A2 | A rare glycogen storage disease due to a deficiency in solute carrier family 2, facilitated glucose transporter member 2 and characterized by hepatorenal glycogen accumulation leading to severe renal tubular dysfunction and impaired glucose and galactose metabolism. | solute carrier family 2 member 2 | ||||
| 185 | Fatty acid hydroxylase-associated neurodegeneration | FA2H | Fatty acid hydroxylase-associated neurodegeneration (FAHN) is characterized early in the disease course by central nervous system involvement including corticospinal tract involvement (spasticity), mixed movement disorder (ataxia/dystonia), and eye findings (optic atrophy, oculomotor abnormalities), and later in the disease course by progressive intellectual impairment and seizures.m. | protocadherin 19 | ||||
| 186 | Female restricted epilepsy with intellectual disability | PCDH19 | Female restricted epilepsy with intellectual disability is a rare X-linked epilepsy syndrome characterized by febrile or afebrile seizures (mainly tonic-clonic, but also absence, myoclonic, and atonic) starting in the first years of life and, in most cases, developmental delay and intellectual disability of variable severity. Behavioral disturbances (e.g. autistic features, hyperactivity, and aggressiveness) are also frequently associated. This disease affects exclusively females, with male carriers being unaffected, despite an X-linked inheritance. | protocadherin 19 | ||||
| 187 | Fibrodysplasia ossificans progressiva | ACVR1 | Fibrodysplasia ossificans progressiva is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that limits movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs. | activin A receptor type 1 | ||||
| 188 | Floating-Harbor syndrom | SRCAP | Snf2 related CREBBP activator protein | |||||
| 189 | Focal facial dermal dysplasia type III | TWIST2 | twist family bHLH transcription factor 2 | |||||
| 190 | Formiminoglutamic aciduria | FTCD | formimidoyltransferase cyclodeaminase | |||||
| 191 | Fragile X syndrome | FMR1 | fragile X messenger ribonucleoprotein 1 | |||||
| 192 | Frasier syndrome | WT1 | WT1 transcription factor | |||||
| 193 | FRAXE intellectual disability | AFF2 | AF4/FMR2 family member 2 | |||||
| 194 | Friedreich ataxia | FXN | frataxin | |||||
| 195 | Fumaric aciduria | FH | fumarate hydratase | |||||
| 196 | Gamma-aminobutyric acid transaminase deficiency | ABAT | 4-aminobutyrate aminotransferase | |||||
| 197 | GAPO syndrome | ANTXR1 | ANTXR cell adhesion molecule 1 | |||||
| 198 | Gardner syndrome | APC | APC regulator of WNT signaling pathway | |||||
| 199 | Giant axonal neuropathy | GAN | gigaxonin | |||||
| 200 | Gingival fibromatosis-hypertrichosis syndrome | 1/175,000 worldwide | ABCA5 | EST90690, ATP-binding cassette, ABC1 member 5 | Gingival fibromatosis-hypertrichosis syndrome (GFHS) is a rare genetic disorder characterized by the overgrowth of gum tissue (gingival fibromatosis) and excessive hair growth (hypertrichosis). It has been linked to mutations in the ABCA5 gene, which encodes a protein involved in the transport of various molecules across cellular membranes. Mutations in this gene can disrupt normal cellular processes, leading to the characteristic features of GFHS. This syndrome often presents in childhood and can significantly affect oral health and appearance due to the excessive growth of gingival tissue and hair. | ATP binding cassette subfamily A member5n | ||
| 201 | Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome | 1 in 100000 individuals | FBN1 | FIBRILIN, FBN, MFS1, MASS | Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome (GEMSS) is a rare genetic disorder caused by mutations in the FBN1 gene. This gene normally provides instructions for making a protein called fibrillin-1, which is essential for the formation of connective tissues. In GEMSS, mutations in FBN1 lead to various clinical features including glaucoma (increased pressure in the eye), ectopia lentis (dislocation of the lens), microspherophakia (abnormally small and spherical lens), joint stiffness, and short stature. The syndrome is inherited in an autosomal recessive manner, meaning both copies of the FBN1 gene must be mutated to manifest the disorder. Treatment typically focuses on managing the symptoms, which can vary in severity among affected individuals. | fibrillin 1 | ||
| 202 | Glomerulopathy with fibronectin deposits 2 | unknown | FN1 | FINC, FN, Fibronectin | Glomerulopathy with fibronectin deposits type 2 (GFND2) is a rare genetic kidney disorder characterized by abnormal deposits of fibronectin protein within the glomeruli, the filtering units of the kidneys. This condition typically presents with proteinuria (excessive protein in the urine), hematuria (blood in the urine), and eventually progresses to chronic kidney disease. GFND2 is caused by mutations in the FN1 gene, which encodes the fibronectin protein. Treatment focuses on managing symptoms and may include medications to control blood pressure and proteinuria, as well as supportive care like dialysis or kidney transplant in advanced cases. | fibrillin 1 | ||
| 203 | Glucose-galactose malabsorption | affect about 1 in 100,000 to 1 in 500,000 individuals worldwide | SLC5A1 | SGLT1, NAGT, D22S675 | Glucose-galactose malabsorption (GGM) is a rare genetic disorder characterized by the inability to absorb glucose and galactose from the intestines. This condition is caused by mutations in the SLC5A1 gene, which affects the function of the sodium-glucose cotransporter 1 (SGLT1) protein responsible for transporting glucose and galactose across the intestinal lining. Symptoms typically appear soon after birth and include severe diarrhea, dehydration, and failure to thrive. Treatment involves strict avoidance of glucose and galactose in the diet, with substitution of other carbohydrates and supportive measures like electrolyte replacement and nutritional support. | Solute carrier family 5 member1 | ||
| 204 | Glutaryl-CoA dehydrogenase deficiency | about 1 in 30,000 to 40,000 newborns worldwide | GCDH | Glutaryl-CoA dehydrogenase, GCD, GCDase | Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare genetic disorder that impairs the body's ability to break down certain amino acids (lysine, hydroxylysine, and tryptophan) from proteins in food. This deficiency leads to an accumulation of toxic compounds, causing damage to the brain and nervous system. Symptoms typically appear during infancy or early childhood and can include developmental delays, movement disorders, seizures, and a progressive decline in motor and cognitive functions. Early detection through newborn screening and prompt medical intervention are crucial for managing the condition and minimizing its effects. | glutaryl-coA dehydrogenase | ||
| 205 | Glycogen storage disease due to LAMP-2 deficiency | 200 cases reported worldwide as of recent. estimates | LAMP2 | CD107b, LGP85, LAMPB | Glycogen storage disease due to LAMP-2 deficiency, also known as Danon disease, is a rare genetic disorder caused by mutations in the LAMP2 gene. This condition affects the body's ability to properly break down and use glycogen, leading to the accumulation of glycogen in various tissues, particularly in the heart, skeletal muscles, and liver. Symptoms typically include cardiomyopathy, muscle weakness, and liver dysfunction, often presenting in childhood or adolescence. The disease is inherited in an X-linked dominant pattern. | Lysosomal associated membrane protein 2 | ||
| 206 | Glycogen storage disease due to LAMP-2 deficiency | unknown | GYS1 | GYS, Glycogen Synthase 1, Glycogen Synthase Liver, Glycogen Synthase 1 (Muscle) | Glycogen synthase is an enzyme responsible for catalyzing the conversion of glucose molecules into glycogen, a form of stored glucose in the body. In GSD type 0, the deficiency of glycogen synthase in muscle and heart tissues impairs the ability to properly store glycogen. This leads to problems in maintaining normal blood sugar levels during periods of fasting or increased energy demand, as glycogen serves as a critical energy reserve.Glycogen storage disease due to muscle and heart glycogen synthase deficiency, related to the GYS1 gene, refers to a genetic condition where mutations in the GYS1 gene lead to deficiencies in the enzyme glycogen synthase. This enzyme is crucial for glycogen synthesis, the storage form of glucose in muscles and the heart. When deficient, glycogen synthesis is impaired, resulting in abnormal accumulation of glycogen in these tissues. | Glycogen Synthase 1 | ||
| 207 | Glycogen storage disease due to muscle glycogen phosphorylase deficiency | unknown | PYGM | PYGM, Myophosphorylase, Muscle Glycogen Phosphorylase, Glycogen Phosphorylase Muscle, | Glycogen storage disease due to muscle glycogen phosphorylase deficiency, specifically known as McArdle disease or Glycogen Storage Disease Type V (GSD V), is a genetic disorder characterized by the inability to break down glycogen in muscle cells. This results in muscle weakness, cramping, and fatigue during exercise, due to the impaired release of glucose from stored glycogen.Glycogen storage disease due to muscle glycogen phosphorylase deficiency (also known as McArdle disease) is caused by mutations in the PYGM gene. This gene provides instructions for making the muscle-specific form of glycogen phosphorylase, which is crucial for breaking down glycogen into glucose in muscle cells. Mutations in the PYGM gene impair this enzyme's function, leading to difficulty in releasing glucose from glycogen during muscle activity. This results in muscle weakness, cramping, and exercise intolerance, among other symptoms. | Glycogen Phosphorylase muscle associated | ||
| 208 | Glycogen storage disease due to phosphoglycerate kinase 1 deficiency | 1 in 1,000,000 individuals worldwide | PGK1 | PGK1, phosphoglycerate Kinase 1, Phosphoglycerate Kinase muscle, PGKA | Glycogen storage disease due to phosphoglycerate kinase 1 (PGK1) deficiency is a rare genetic disorder caused by mutations in the PGK1 gene, which encodes the enzyme phosphoglycerate kinase 1. This enzyme plays a crucial role in the glycolytic pathway, where it catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, generating ATP.Individuals with PGK1 deficiency typically present with symptoms related to impaired energy production in cells, particularly affecting tissues with high energy demands such as muscle and brain. Common clinical features may include exercise intolerance, muscle weakness (myopathy), neurological abnormalities, and hemolytic anemia (due to red blood cell breakdown).The severity and specific symptoms can vary widely among affected individuals, often depending on the specific mutation and its impact on enzyme function. The inheritance pattern is typically X-linked recessive, meaning the condition predominantly affects males, while females are typically carriers. | Phosphoglyecerate Kinase 1 | ||
| 209 | Gollop-Wolfgang complex | unknown | BHLHA9 | Cartilage-associated protein (CRTAP), Basic helix-loop-helix family, member a9 (bHLHa9), bHLH transcription factor A9 | The Gollop-Wolfgang complex is a rare genetic condition marked by abnormalities in bone development, particularly fusion of ribs to the spine and limb defects like split hand/foot malformation. It is congenital and varies in severity, impacting skeletal structure and limb formation. The Gollop-Wolfgang complex is a rare congenital malformation characterized by the presence of bifid femora and other limb abnormalities. It is associated with mutations in the BHLHA9 gene. The BHLHA9 gene plays a critical role in the development of the limbs, and its mutations disrupt normal limb formation, leading to the phenotypic manifestations seen in this complex. | Basic helix-100 P-helix family member a9 | ||
| 210 | Gray platelet syndrome | 60 cases have been reported worldwide. | NBEAL2 | ELTRA (ELT-2A), EHRLICHIOSIS-RELATED GENE (ERG2), NBEAL2 (Neurobeachin-like 2 | Gray Platelet Syndrome (GPS) is a rare inherited bleeding disorder characterized by platelets that appear gray under a microscope due to a deficiency in alpha granules, which are storage compartments in platelets containing proteins crucial for normal clotting. Here are some key points about GPS. The syndrome is caused by mutations in the NBEAL2 gene. This gene provides instructions for producing a protein involved in the formation and maintenance of alpha granules in platelets. Mutations in NBEAL2 disrupt the function of this protein, leading to the characteristic large, gray-appearing platelets seen under a microscope due to the absence of alpha granules. | Neurobeachin like 2 | ||
| 211 | Greig cephalopolysyndactyly syndrome | estimated range 1-9/1,000,000 | GLI3 | GLI-Kruppel family member3, GLI3 zinc finger protein, GCPS, PHS (Pallister-Hall syndrome), ZNF165 | Greig Cephalopolysyndactyly syndrome (GCPS) is a rare genetic disorder characterized by distinctive facial features, extra fingers or toes (polydactyly), and fused fingers or toes (syndactyly). It is caused by mutations in the GLI3 gene and typically inherited in an autosomal dominant pattern. | GLI family zinc finger3 | ||
| 212 | Griscelli syndrome type 1 | unknown | MYO5A | MYO5, Myosin-V, Myosin heavy chain 12, Dilute (Dil), Dilute myosin heavy chain | Griscelli Syndrome type 1 (GS1) is a rare genetic disorder characterized by partial albinism and neurological impairment. It is caused by mutations in the MYO5A gene, which affect the transport of melanosomes and other organelles within cells. Symptoms include silvery-gray hair, light skin, and severe neurological deficits such as developmental delay and seizures. GS1 is typically diagnosed in infancy or early childhood and requires genetic testing for confirmation. | Myosin VA | ||
| 213 | Growth delay due to insulin-like growth factor I resistance | unknown | IGF1R | CD221, IGFIR, JTK13, IGFR, Insulin-like growth factor 1 receptor precursor | Growth delay due to insulin-like growth factor 1 (IGF-1) resistance is a condition where the body's tissues are less responsive to IGF-1, a hormone crucial for growth and development. This resistance can lead to poor growth in children, resulting in short stature and delayed physical development. It may be caused by genetic mutations affecting the IGF1R gene, which encodes the IGF-1 receptor, or other factors disrupting the IGF-1 signaling pathway. Diagnosis typically involves clinical evaluation, growth measurements, and genetic testing. Treatment may include IGF-1 therapy to promote growth. | Insulin like growth factor 1 receptor | ||
| 214 | H syndrome | only 100-120 patients with H syndrome have been found worldwide | SLC29A3 | ENT3 HUP1 SPG33 Ros1 hENT3 | H syndrome, also known as H syndrome or hyperpigmentation, hypertrichosis, and hepatosplenomegaly syndrome, is a rare genetic disorder characterized by several distinctive features. It is caused by mutations in the SLC29A3 gene, which encodes a protein involved in the transport of nucleosides across cell membranes.clinical features and systemic manifestations including cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, hearing loss, heart anomalies,hypogonadism, hyperglycaemia, low height, and hallux valgus. | solute carrier family 29 member 3 | ||
| 215 | Heart defect-tongue hamartoma-polysyndactyly syndrome | Fewer than 1,000 people in the U.S. have thisdisease. | WDPCP | BBS15 CPLANE5 C2orf86 Fritz WD Repeat-Containing And Planar Cell Polarity Effector Protein Fritz Homolog Ciliogenesis And Planar Polarity Effector Complex Subunit Bardet-Biedl Syndrome 15 Protein HFrtz WD Repeat-Containing And Planar Cell Polarity Effector Protein 4 Ciliogenesis And Planar Polarity Effector WD Repeat-Containing Protein C2orf86 Chromosome 2 Open Reading Frame 86 | A rare genetic multiple congenital anomalies syndrome with characteristics of congenital heart defects (for example coarctation of the aorta with or without atrioventricula r canal and subaortic stenosis), associated with tongue hamartomas, postaxial hand polydactyly and toe syndactyly. There is evidence the disease is caused by compound heterozygous mutation in the WDPCP gene on chromosome 2p15. | WD repeat containing planar cell polarity effector | ||
| 216 | Hemochromatosis type 4 | Fewer than 1,000 people in the U.S. have thisdisease. | SLC40A1 | Ferroportin-1 IREG1 MTP1 Fpn1 | Hemochromatosis type 4 (also called ferroportin disease) is a disease in which too much iron builds up in the body. This is also called iron overload. Accumulation of iron in the organs is toxic and can cause organ damage. While many organs can be affected, iron overload is especially likely to affect the liver, heart, and pancreas.Hemochromatosis type 4A Hemochromatosis type 4B People with Hemochromatosis type 4A might not have any symptoms of the disease. Other individuals may develop liver disease as they get older. Hemochromatosis type 4B can be associated with fatigue, weakness, and joint pain. Other symptoms may include abdominal pain, loss of sex drive, liver disease, diabetes, heart problems, difficulty breathing, and skin discoloration. Symptoms of Hemochromatosis type 4B can begin anytime from childhood to adulthood. Hemochromatosis type 4 is most common in people of southern European ancestry. Hemochromatosis type 4 is caused by genetic changes (genetic changes or pathogenic variants) to the SLC40A1 gene. The disease is inherited in an autosomal dominant manner. | solute carrier family 40 member 1 | ||
| 217 | Hemoglobin C disease | HBB | Hemoglobin C is a common hemoglobin variant that has a single amino acid substitution (lysine substituted for the glutamate) in the sixth position of the beta-globin chain. The patients with hemoglobin C trait (HbAC) are phenotypically normal, while patients with hemoglobin C disease (HbCC) may have chronic hemolytic anemia. This activity reviews the evaluation and management of hemoglobin C disease and highlights the role of the interprofessional team in improving care for patients with this condition.. | hemoglobin subunit beta | ||||
| 218 | Hemoglobin E disease | HBB | Hemoglobin E (HbE) disease is a mild, inherited blood disorder characterized by an abnormal form of hemoglobin, called hemoglobin E. People with this condition may have very mild anemia, but the condition typically does not cause any symptoms. It is inherited in an autosomal recessive manner and is caused by a genetic change in the HBB gene. | hemoglobin subunit beta | ||||
| 219 | Hepatoerythropoietic porphyria | UROD | Hepatoerythropoietic porphyria (HEP) is an extremely rare genetic disorder characterized by deficiency of the enzyme, uroporphyrinogen decarboxylase. This deficiency is caused by mutations of both copies of a person’s UROD gene, which means that the disorder is inherited as an autosomal recessive trait. Most affected individuals have a profound deficiency of this enzyme and onset of the disorder is usually during infancy or early childhood. | uroporphyrinogen decarboxylase | ||||
| 220 | Hereditary continuous muscle fiber activity | Unknown | KCNA1 | Kv1.1 HBK1 MK-1 Kv1.1-alpha | Hereditary continuous muscle fiber activity is a rare muscle disease that causes muscle twitching and increased muscle tension throughout the body. This can lead to difficulty with movement, including walking, and delayed development of motor skills. Other symptoms may include stiffness in the legs, a spastic gait, and increased reflexes. The condition may be worsened by fever or anesthesia | potassium voltage-gated channel subfamily A member 1 | ||
| 221 | Hereditary cryohydrocytosis with normal stomatin | SLC4A1 | Cryohydrocytosis (CHC) is an exceedingly rare condition characterized by a mild stomatocytic hemolytic state with hyperbilirubinemia. A hallmark of this condition is that red blood cells (RBCs) lyse on storage at 4 degrees centigrade. RBC cation permeability is increased at 37 degrees centigrade, and the cells also accumulate sodium in the cold (summary by Coles et al., 1999). Patients present with fatigue, mild anemia, and pseudohyperkalemia due to a potassium leak from the RBCs (summary by Bogdanova et al., 2010). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses, | solute carrier family 4 member 1 (Diego blood group) | ||||
| 222 | Hereditary folate malabsorption | Unknown | SLC46A1 | PCFT (Proton-Coupled Folate Transporter) RFC4 (Reduced Folate Carrier 4) FRCP (Folate Receptor Chimeric Protein) FOLT (Folate Transporter) | Hereditary folate malabsorption (HFM) is characterized by folate deficiency due to impaired intestinal folate absorption and impaired folate transport into the central nervous system. Findings include poor feeding, failure to thrive, and anemia. There can be leukopenia and thrombocytopenia, diarrhea and/or oral mucositis, hypoimmunoglobulinemia, and other immunologic dysfunction resulting in infections, most often Pneumocystis jirovecii pneumonia. Neurologic manifestations include developmental delays, cognitive and motor disorders, behavioral disorders, and seizures. | solute carrier family 46 member 1 | ||
| 223 | Hereditary leiomyomatosis and renal cell cancer | FH | Cryohydrocytosis (CHC) is an exceedingly rare condition characterized by a mild stomatocytic hemolytic state with hyperbilirubinemia. A hallmark of this condition is that red blood cells (RBCs) lyse on storage at 4 degrees centigrade. RBC cation permeability is increased at 37 degrees centigrade, and the cells also accumulate sodium in the cold (summary by Coles et al., 1999). Patients present with fatigue, mild anemia, and pseudohyperkalemia due to a potassium leak from the RBCs (summary by Bogdanova et al., 2010). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses | fumarate hydratase | ||||
| 224 | Hereditary myopathy with early respiratory failure | TTN | GMD2J CMPD4 MYLK5 CMH9 TMD Rhabdomyosarcoma Antigen MU-RMS-40. Connectin FLJ32040 CMD1G Cardiomyopathy, Dilated 1G (Autosomal Dominant) LGMDR10 CMYP5 EOMFC HMERF SALMY | Hereditary myopathy with early respiratory failure (HMERF) is a rare genetic disorder characterized by progressive muscle weakness and early respiratory insufficiency. HMERF is primarily caused by mutations in the TTN gene (titin), which is one of the largest known human genes encoding a muscle protein involved in muscle contraction and elasticity. | Titin | |||
| 225 | Hydroxykynureninuria | KYNU | Hydroxykynureninuria, also known as xanthurenicaciduria, is an autosomal recessive condition characterized by high urinary excretion of kynurenine (KYN), xanthurenic acid (XA) and 3-hydroxykynurenine (3-OHKYN), with no detectable anthranilic acid (AA) or 3-hydroxyanthranilic acid (3-OHAA) | kynureninase | ||||
| 226 | Hypobetalipoproteinemia, familial, 1 | APOB | Individuals with biallelic APOB-related familial hypobetalipoproteinemia (APOB-FHBL) may present from infancy through to adulthood with a range of clinical symptoms including deficiency of fat-soluble vitamins and gastrointestinal and neurologic dysfunction. Affected individuals typically have plasma total cholesterol, LDL cholesterol, and apo B levels below the fifth centile for age and sex. Acanthocytosis, elevated liver enzymes, and hyperbilirubinemia may also be found. The most common clinical findings are hepatomegaly, steatorrhea, and failure to thrive / growth deficiency. In the absence of treatment, affected individuals can develop atypical pigmentation of the retina; progressive loss of deep tendon reflexes, vibratory sense, and proprioception; muscle pain or weakness; dysarthria; ataxia; tremors; and steatohepatitis, fibrosis, and rarely, cirrhosis of the liver. | apolipoprotein B | ||||
| 227 | Hypocomplementemic urticarial vasculitis | DNASE1L3 | A rare immune complex-mediated small vessel vasculitis characterized by urticaria and hypocomplementemia (low C3, C4 and/or C1q), and usually associated with circulating anti-C1q autoantibodies. Arthritis, pulmonary disease, ocular inflammation are common systemic manifestations. | deoxyribonuclease 1 like 3 | ||||
| 228 | Hypogonadotropic hypogonadism 7 with or without anosmia | GNRHR | A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin- releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism | gonadotropin releasing hormone receptor | ||||
| 229 | Hypopigmentation-punctate palmoplantar keratoderma syndrome | ENPP1 | Cole disease (COLED) is a rare autosomal dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show nonspecific changes including hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or early-onset calcific tendinopathy. | ectonucleotide pyrophosphatase/phosphodiesterase 1 | ||||
| 230 | Ichthyosis hystrix of Curth-Macklin | KRT1 | The skin is usually normal at birth. The disease starts in early childhood with severe hyperkeratosis of yellow-brown or grey color, and of spiky, cobblestone-like (hystrix) or verrucous appearance. Hyperkeratosis is often diffuse and more pronounced on extensor areas of the limbs, extremities and the trunk. Lesions may also be nevoid following the lines of Blaschko. Patients are also affected with striate or diffuse PPK. As the disease progresses, PPK worsens and results in deep bleeding, painful fissures and cracks. In severe cases, PPK can also lead to contractures, gangrene and loss of digits. The skin is malodorous and frequently infected. Nail dystrophy may be present. Contrary to other keratinopathic ichthyoses, no skin fragility/blister formation or erythroderma is present. | keratin 1 | ||||
| 231 | Idiopathic CD4 lymphocytopenia | UNC119 | Idiopathic CD4 lymphocytopenia is a rare primary immunodeficiency disorder characterized by persistent CD4 T-cell lymphopenia (less than 300 cells/µL on multiple occasions) not associated with any other underlying primary or secondary immune deficiency. Patients typically present opportunistic infections (with cryptococcal, mycobacterial, candidal, varicella zoster virus infections and progressive multifocal leukoencephalopathy being the most prevalent), malignancies (mainly lymphoproliferative disorders), or autoimmune disorders. Some individuals are asymptomatic and incidentally diagnosed. | unc-119 lipid binding chaperone | ||||
| 232 | Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly | MRPL44 | A rare mitochondrial oxidative phosphorylation disorder with complex I and IV deficiency characterized by hypertrophic cardiomyopathy, hepatic steatosis with elevated liver transaminases, exercise intolerance and muscle weakness. Neuro-opthalmological features (hemiplegic migraine, Leigh-like lesions on brain MRI, pigmentary retinopathy) have been reported later in life. | mitochondrial ribosomal protein L44 | ||||
| 233 | Infantile hypertrophic cardiomyopathy due to MRPL44 deficiency | MRPL44 | A rare mitochondrial oxidative phosphorylation disorder with complex I and IV deficiency characterized by hypertrophic cardiomyopathy, hepatic steatosis with elevated liver transaminases, exercise intolerance and muscle weakness. Neuro-opthalmological features (hemiplegic migraine, Leigh-like lesions on brain MRI, pigmentary retinopathy) have been reported later in life. | mitochondrial ribosomal protein L44 | ||||
| 234 | Infantile osteopetrosis with neuroaxonal dysplasia | OSTM1 | osteoclastogenesis associated transmembrane protein 1 | |||||
| 235 | Infantile systemic hyalinosis | ANTXR2 | ANTXR cell adhesion molecule 2 | |||||
| 236 | Infantile-onset periodic fever-panniculitis-dermatosis syndrome | OTULIN | OTU deubiquitinase with linear linkage specificity | |||||
| 237 | Intellectual developmental disorder, autosomal dominant 29 | SETBP1 | SET binding protein 1 | |||||
| 238 | Intellectual developmental disorder, autosomal dominant 29 | HIVEP2 | HIVEP zinc finger 2 | |||||
| 239 | Intellectual developmental disorder, autosomal dominant 6, with or without seizures | GRIN2B | glutamate ionotropic receptor NMDA type subunit 2B | |||||
| 240 | Intellectual developmental disorder, x-linked, syndromic, turner type | HUWE1 | HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 | |||||
| 241 | Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome | PACS1 | phosphofurin acidic cluster sorting protein 1 | |||||
| 242 | Intellectual disability-hypotonic facies syndrome, x-linked, 1 | around 1 in 1,000,000 individuals | ATRX | XH2, RAD54, RAD54L, ADD, JAL, SMAXC | Intellectual Disability-Hypotonic Facies Syndrome, X-Linked, 1 (MRXHF1) is a genetic disorder characterized by intellectual disability, distinctive facial features with low muscle tone, and often includes other neurological and developmental abnormalities. This syndrome is caused by mutations in the ATRX gene located on the X chromosome. | ATRX chromatin remodeler | ||
| 243 | Intellectual disability-severe speech delay-mild dysmorphism syndrome | 1 in 1,000,000 individuals worldwide | FOXP1 | FOXP1 | The syndrome you're referring to seems to describe a condition characterized by intellectual disability, severe speech delay, and mild dysmorphism (which refers to minor physical abnormalities or features). This combination suggests a complex interplay of developmental and genetic factors affecting cognitive and speech functions, alongside subtle physical differences. Specific diagnoses and further details would typically require a medical evaluation by a healthcare professional familiar with developmental disorders and genetic syndromes. | forkhead box P1 | ||
| 244 | Intellectual disability-severe speech delay-mild dysmorphism syndrome | 1 in 1,000,000 individuals worldwide | FOXP1 | FOXP1 | The syndrome you're referring to seems to describe a condition characterized by intellectual disability, severe speech delay, and mild dysmorphism (which refers to minor physical abnormalities or features). This combination suggests a complex interplay of developmental and genetic factors affecting cognitive and speech functions, alongside subtle physical differences. Specific diagnoses and further details would typically require a medical evaluation by a healthcare professional familiar with developmental disorders and genetic syndromes. | forkhead box P1 | ||
| 245 | Isolated congenital adermatoglyphia | unknown | SMARCAD1 | ACF1 | Isolated congenital adermatoglyphia, also known as "immigration delay disease," is a rare genetic condition characterized by the absence of fingerprints from birth. This anomaly is typically caused by mutations in the SMARCAD1 gene, which is involved in skin development. Besides the lack of fingerprints, affected individuals generally have no other health issues related to the condition. | SWI/SNF- related,matrix-associated actin-dep endentregulator of chromatin | ||
| 246 | Isolated congenital breast hypoplasia/aplasia | PTPRF | protein tyrosine phosphatase receptor type F | |||||
| 247 | Juvenile absence epilepsy | 1 in 20,000 to 30,000 worldwide | EFHC1 | EFHC1, EFHC, Joubert syndrome-related protein 9 (JBTS9), Seizure-related gene 6 (SEZ-6) | Isolated congenital breast hypoplasia/aplasia is a rare congenital condition characterized by the underdevelopment (hypoplasia) or absence (aplasia) of breast tissue in individuals. This condition can affect one or both breasts and is present from birth.The EFHC1 gene (EF-hand domain containing 1) has been implicated in various neurological conditions, but its role in congenital breast hypoplasia/aplasia is less clear. Mutations in the EFHC1 gene are more commonly associated with juvenile myoclonic epilepsy, where they can disrupt normal brain function. | EF-hand domain containing 1 | ||
| 248 | Juvenile Huntington disease | unknown | HTT | HD (Huntington Disease gene), IT15 (Interesting Transcript 15), HTT1 | Juvenile Huntington Disease (JHD) is a rare, early-onset form of Huntington's Disease that typically manifests before the age of 20. JHD is characterized by symptoms such as movement disorders, cognitive decline, and psychiatric issues. The disease progresses more rapidly compared to adult-onset Huntington's Disease.The genetic basis of JHD is a mutation in the HTT gene, which involves an expanded CAG repeat in the gene's coding region. This mutation leads to the production of an abnormal huntingtin protein, resulting in neuronal dysfunction and degeneration. | hantingtin | ||
| 249 | Kaposiform hemangioendothelioma | unknown | GNA14 | Guanine Nucleotide Binding Protein (G Protein), Alpha 14G-Alpha-14, GNA-14 | Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that typically occurs in infants and young children. It is characterized by aggressive, locally invasive growth and can be associated with a severe coagulopathy known as Kasabach-Merritt phenomenon.KHE has been linked to mutations in the GNA14 gene, which is involved in signaling pathways that regulate cell proliferation and differentiation. | G protein subunit alpha 14 | ||
| 250 | KCNQ2-related epileptic encephalopathy | ~100 new infants per year in the USn | KCNQ2 | Kv7.2, Voltage-Gated Potassium Channel Subunit Kv7.2, ENFL1 (Epilepsy, Neonatal, Familial, 1), BFNS (Benign Familial Neonatal Seizures) | KCNT2-related epileptic encephalopathy is a severe neurological disorder caused by mutations in the KCNT2 gene. This gene encodes a potassium channel critical for regulating neuronal excitability. Mutations lead to dysfunctional potassium channels, resulting in frequent, severe seizures and significant developmental delays, cognitive impairment, and various neurological deficits. This condition typically manifests in early infancy or childhood. | potassium voltage-g ated channel subfamily Qmember2 | ||
| 251 | Kennedy disease | AR | androgen receptor | |||||
| 252 | Keratolytic winter erythema | prevalence of 1/7,000 in the South African Afrikaans-speaking Caucasoid population | CTSB | APP secretase Cathepsin B1 EC 3.4.22.1 CPSB CSTB | Keratolytic winter erythema (KWE) is a rare autosomal dominant keratoderma affecting primarily the palms and soles, manifesting with recurrent waves of erythema followed byepidermal peeling. The condition is so named in view of its anecdotal worsening during the winter months. Skin lesions may spread to the dorsum of hands and feet and to the interdigital spaces. Lower legs, knees and thighs may also be involved. Episodes may be preceded by itch and hyperhidrosis.In the presence of the duplication, CTSB gene expression is elevated in the stratum granulosum of affected individuals | cathepsin B | ||
| 253 | Keratosis palmoplantaris striata ii | KRT1 | keratin 1 | |||||
| 254 | King-Denborough syndrome | RYR1 | RYR Skeletal Muscle Ryanodine Receptor RyR1 Calcium Release Channel Skeletal Muscle Calcium Release Channel Skeletal Muscle Ryanodine Receptor 1 MHS MHS1 (Malignant Hyperthermia Susceptibility 1) SKRR (Skeletal Muscle Ryanodine Receptor) CAVS (Central Core Disease-related variants in Ryanodine Receptor) | King-Denborough syndrome (KDS) is a rare congenital myopathy characterized by a combination of clinical features including muscle weakness, susceptibility to malignant hyperthermia, and distinctive facial features. It is also sometimes associated with skeletal abnormalities and intellectual disabilities. some cases have been attributed to the ryanodine receptor gene (RYR1), which has been tied to malignant hyperthermia and central core disease. | ryanodine receptor 1 | |||
| 253 | Keratosis palmoplantaris striata ii | KRT1 | keratin 1 | |||||
| 254 | King-Denborough syndrome | RYR1 | RYR Skeletal Muscle Ryanodine Receptor RyR1 Calcium Release Channel Skeletal Muscle Calcium Release Channel Skeletal Muscle Ryanodine Receptor 1 MHS MHS1 (Malignant Hyperthermia Susceptibility 1) SKRR (Skeletal Muscle Ryanodine Receptor) CAVS (Central Core Disease-related variants in Ryanodine Receptor) | King-Denborough syndrome (KDS) is a rare congenital myopathy characterized by a combination of clinical features including muscle weakness, susceptibility to malignant hyperthermia, and distinctive facial features. It is also sometimes associated with skeletal abnormalities and intellectual disabilities. some cases have been attributed to the ryanodine receptor gene (RYR1), which has been tied to malignant hyperthermia and central core disease. | ryanodine receptor 1 | |||
| 255 | KRT1-related diffuse nonepidermolytic keratoderma | KRT1 | keratin 1 | |||||
| 256 | Laminin subunit alpha 2-related congenital muscular dystrophy | between 1 in 50,000 and 1 in 400,000 individuals worldwide. | LAMA2 | Laminin alpha-2 Laminin subunit alpha-2 Merosin Laminin-2 Laminin, alpha 2 Laminin M chain LAMA | Laminin subunit alpha 2-related congenital muscular dystrophy (LAMA2-CMD) is a genetic disorder caused by mutations in the LAMA2 gene, which encodes the alpha-2 chain of laminin. Early-onset LAMA2-related muscular dystrophy is apparent at birth or within the first few months of life. It is considered part of a class of muscle disorders called congenital muscular dystrophies and is sometimes called congenital muscular dystrophy type 1A. Affected infants may have severe muscle weakness, lack of muscle tone (hypotonia), little spontaneous movement, and joint deformities (contractures). | laminin subunit alpha 2 | ||
| 257 | Larsen syndrome | FLNB | filamin B | |||||
| 258 | Late-onset distal myopathy, Markesbery-Griggs type | LDB3 | LIM domain binding 3 | |||||
| 259 | Late-onset retinal degeneration | C1QTNF5 | TRP5 Complement C1q Tumor Necrosis Factor-Related Protein C1q And Tumor Necrosis Factor Related Protein Myonectin LORD Complement-C1q Tumor Necrosis Factor-Related Protein Membrane Frizzled-Related Protein C1q TNF-Alpha-Related Protein MFRP | C1q and TNF related 5 | ||||
| 260 | Lathosterolosis | The condition has been documented in only a few individuals worldwide | SC5D | Sterol-C5-desaturase Lathosterol oxidase SC5DL | Lathosterolosis is an inborn error of cholesterol biosynthesis due to deficiency of the enzyme 3-beta-hydroxysteroid-delta-5-desaturase (or sterol-C5- desaturase or SC5D). It is an autosomal recessive disorder .This results in a defect in conversion of lathosterol into 7-dehydrocholesterol. Lathosterolosis were characterized by multiple congenital anomalies, learning disability, and liver involvement. | sterol-C5-desaturase | ||
| 261 | Laurence-Moon syndrome | around 1 in 100,000 to 1 in 160,000 live births globally. | PNPLA6 | NTE Neuropathy Target Esterase IPLA2delta Sws Patatin-Like Phospholipase Domain-Containing Protein Patatin-Like Phospholipase Domain Containing NTEMND BNHS LNMS OMCS | Laurence-Moon-Bardet-Biedl syndrome (LMBBS), a rare autosomal recessive genetic disorder, tends to bring about an array of multiorgan detrimental manifestations . LMBBS patients may encounter deteriorating functions of the brain, eyes, kidneys, hands, and feet. The primary features of this syndrome include retinal dystrophy, polydactyly, obesity, hypogonadism, renal abnormalities, and mental retardation. However, LMBBS may also present with other secondary abnormalities, including speech disorder and developmental delay, ataxia, diabetes insipidus, and dental crowding | patatin like phospholipase domain containing 6 | ||
| 262 | Laurin-Sandrow syndrome | LMBR1 | Laurin-Sandrow syndrome (LSS) is characterised by complete polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella), often associated with ulnar and/or fibular duplication (and sometimes tibial agenesis). It has been described in less than 20 cases. Some cases with the same clinical signs but without nasal defects have also been reported, and may represent the same entity. The etiology of LSS is unknown. | limb development membrane protein 1 | ||||
| 263 | Leydig cell hypoplasia due to LHB deficiency | LHB | A rare 46,XY difference of sex development due to impaired androgen production characterized by impaired normal male sexual development. The severity of the disorder varies and can manifest in its severe form with complete 46,XY male pseudohermaphroditism, including low testosterone and high luteinizing hormone levels, absent development of secondary male sex characteristics and lack of breast development. Patients with the milder form can have a wider range of phenotypes, ranging from micropenis to severe hypospadias. | luteinizing hormone subunit beta | ||||
| 264 | Lipodystrophy, congenital generalized, type 3 | CAV1 | Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis, and early onset of diabetes. | caveolin 1 | ||||
| 265 | Lipodystrophy, congenital generalized, type 4 | CAVIN1 | A form of congenital generalized lipodystrophy, a metabolic disorder characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and diabetes mellitus. CGL4 is characterized by the association of congenital generalized lipodystrophy with muscular dystrophy and cardiac anomalies. Inheritance is autosomal recessive. | caveolae associated protein 1 | ||||
| 266 | Lipoic acid synthetase deficiency | LIAS | A rare neurometabolic disease characterized by a neonatal onset of seizures (often intractable), muscular hypotonia, feeding difficulties (poor sucking and/or swallowing) and mild to severe psychomotor delay, associated with nonketotic hyperglycinemia typically revealed by biochemical analysis. Respiratory problems (apnea, acute respiratory acidosis), lethargy, hearing loss, microcephaly and spasticity with pyramidal signs may also be associated. | caveolae associated protein 1 | lipoic acid synthetase | |||
| 267 | Localized dystrophic epidermolysis bullosa, pretibial form | COL7A1 | A localized form of dystrophic epidermolysis bullosa characterized by blisters confined primarily to the hands and feet (acral form) or to the pretibial region (pretibial form). Nail dystrophy or loss is common and may be an isolated finding (nail only form). This disease can be inherited via autosomal dominant or autosomal recessive inheritance. | collagen type VII alpha 1 chain | ||||
| 268 | Loeys-dietz syndrome 1 | TGFBR1 | A gene change (mutation) causes Loeys-Dietz syndrome. This connective tissue disease enlarges the aorta, raising the risk of aortic aneurysms, dissections and ruptures. It also affects the bones, eyes and skin. The condition is similar to Marfan syndrome. Ongoing screenings and blood pressure medications lower the risk of life-threatening problems. | transforming growth factor beta receptor 1 | ||||
| 269 | Long qt syndrome 5 | KCNE1 | Long QT syndrome is a disorder of cardiac repolarization characterized clinically by prolongation of the QT interval and heart rate–corrected QT value (QTc) (Figure 1A) on the surface electrocardiogram (ECG) and a predilection for torsadogenic syncope/seizures and sudden cardiac arrest or death (SCA/SCD) | potassium voltage-gated channel subfamily E regulatory subunit 1 | ||||
| 270 | Long qt syndrome 9 | CAV3 | Long QT syndrome (LQTS) is a cardiac electrophysiologic disorder, characterized by QT prolongation and T-wave abnormalities on the EKG that are associated with tachyarrhythmias, typically the ventricular tachycardia torsade de pointes (TdP). TdP is usually self-terminating, thus causing a syncopal event, the most common symptom in individuals with LQTS. Such cardiac events typically occur during exercise and emotional stress, less frequently during sleep, and usually without warning. In some instances, TdP degenerates to ventricular fibrillation and causes aborted cardiac arrest (if the individual is defibrillated) or sudden death. | caveolin 3 | ||||
| 271 | Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome | MTOR | A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability, characterized by macrocephaly, intellectual disability, seizures, dysmorphic facial features (including tall forehead, downslanting palpebral fissures, hypertelorism, depressed nasal bridge, and macrostomia), megalencephaly, and small thorax. Other reported features are umbilical hernia, muscular hypotonia, global developmental delay, autistic behavior, and café-au-lait spots, among others. | mechanistic target of rapamycin kinase | ||||
| 272 | MAGEL2-related Prader-Willi-like syndrome | MAGEL2 | A rare Prader-Willi-like syndrome characterized by arthrogryposis, including contractures of the proximal and distal interphalangeal joints, and autism spectrum disorder due to MAGEL2 mutation. Overlapping phenotypes with Prader-Willi syndrome include hypotonia, feeding difficulties, weigth gain, developmental delay, intellectual disability and hypogonadism. Minority of patients manifest hyperphagia and morbid obesity in contrast to patients with Prader-Willi syndrome. | MAGE family member L2 | ||||
| 273 | Majeed syndrome | LPIN2 | Majeed syndrome is a rare genetic multisystemic disorder characterized by chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, which may be accompanied by neutrophilic dermatosis. | lipin 2 | ||||
| 274 | Malonic aciduria | MLYCD | Malonic aciduria is a metabolic disorder caused by deficiency of malonyl-CoA decarboxylase (MCD).This condition usually presents in early childhood and the manifestations are variable. The majority of patients are developmentally delayed with other features that include hypotonia, seizures, hypoglycaemia, metabolic acidosis, cardiomyopathy and diarrhoea. | malonyl-CoA decarboxylase | ||||
| 275 | Marfan syndrome type 1 | FBN1 | Marfan syndrome affects the connective tissue that holds your body together. Since this condition affects various parts of the body, you’ll need to have appointments with a number of healthcare providers who are experts in these areas. Treatments help people with Marfan syndrome live longer. | fibrillin 1 | ||||
| 276 | Marfan syndrome type 1 | FBN1 | Marfan syndrome affects the connective tissue that holds your body together. Since this condition affects various parts of the body, you’ll need to have appointments with a number of healthcare providers who are experts in these areas. Treatments help people with Marfan syndrome live longer. | fibrillin 1 | ||||
| 277 | McLeod neuroacanthocytosis syndrome | XK | McLeod neuroacanthocytosis syndrome (MLS) is a form of neuroacanthocytosis (see this term) and is characterized clinically by a Huntington's disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, and biochemically by absence of the Kx antigen and by weak expression of the Kell antigens. | X-linked Kx blood group | ||||
| 278 | Meacham syndrome | WT1 | Meacham syndrome is a multiple malformation syndrome characterized by congenital diaphragmatic abnormalities, genital defects and cardiac malformations.Ambiguous or female external genitalia are present in individuals with 46,XY karyotype. The genital abnormalities are variable and may include a true double vagina or septate vagina, absent uterus, abnormal male gonads in the presence of normal external female genitalia or male pseudohermaphroditism with abnormal internal female genitalia. Complex cyanotic congenital heart defects, (hypoplastic right lungs, anomalous pulmonary venous return and abnormalities of the diaphragm) are frequent. One patient with rhabdomyomatous dysplasia of the lungs has been reported. | WT1 transcription factor | ||||
| 279 | Medullary sponge kidney | HNF1B | In medullary sponge kidney, cysts develop in the medulla, or middle area, of your kidney. Usually it does not cause symptoms but some people may develop urinary tract infections or kidney stones. You can prevent these complications with medications and changes to your diet. | HNF1 homeobox B | ||||
| 280 | Megalencephaly-capillary malformation-polymicrogyria syndrome | PIK3CA | Megalencephaly-capillary malformation syndrome (MCAP), formerly known as macrocephaly-capillary malformation, is a complex disorder that involves many organ systems including the skin, blood vessels, connective tissue, brain and others, and that usually manifests at birth. i. Most affected individuals have a disproportionately large head and vascular malformations including capillary malformations on the skin of the midline face, trunk and limbs. These capillary malformations often show a lacy or reticulated pattern (resembling a net or web, and are sometimes termed “cutis marmorata”). Most children with MCAP have an enlarged brain (or megalencephaly) and other findings on brain MRI scans with associated neurological problems. | phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha | ||||
| 281 | Meige disease | EPHB4 | Meige syndrome is a rare neurological movement disorder characterized by involuntary and often forceful contractions of the muscles of the jaw and tongue (oromandibular dystonia) and involuntary muscle spasms and contractions of the muscles around the eyes (blepharospasm). The specific symptoms and their severity vary from case to case. | EPH receptor B4 | ||||
| 282 | Mesoaxial synostotic syndactyly with phalangeal reduction | BHLHA9 | A rare non-syndromic syndactyly characterized by mesoaxial reduction of fingers, complete syndactyly of the 3rd and 4th fingers with synostoses of the corresponding metacarpals and associated single phalanges, malformed thumbs, and hypoplasia and clinodactyly of the 5th finger. Preaxial webbing of toes with terminal phalangeal hypoplasia of all toes has been reported in association. | basic helix-loop-helix family member a9 | ||||
| 283 | Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome | RUNX2 | Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome is characterized by metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait. | RUNX family transcription factor 2 | ||||
| 284 | Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome | MTR | Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome is characterized by metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait. | 5-methyltetrahydrofolate-homocysteine methyltransferase | ||||
| 285 | Microcytic anemia with liver iron overload | SLC11A2 | A congenital hypochromic microcytic anemia with progressive liver iron overload paradoxically associated with normal to moderately elevated serum ferritin levels has been described in three unrelated patients. | solute carrier family 11 member 2 | ||||
| 286 | MORM syndrome | INPP5E | A rare genetic syndromic intellectual disability characterized by language delay and mild to moderate intellectual disability associated with truncal obesity, congenital nonprogressive retinal dystrophy with poor night vision and reduced visual acuity, and micropenis in males. Cataracts may occur in the second or third decade of life. | inositol polyphosphate-5-phosphatase E | ||||
| 287 | MUC1-related autosomal dominant tubulointerstitial kidney disease | MUC1 | A rare autosomal dominant tubulointerstitial kidney (ADTKD) disease due to MUC1 mutations characterized clinically by a bland urinalysis (absence of blood or protein in the urine), and chronic kidney disease leading to end-stage kidney disease (ESKD) between 20 and 80 years.Chronic kidney disease usually is first evident in the early twenties. Patients will have slowly progressive loss of kidney function, between 1 and 3 ml/min/1.73m2/year. The mean age of ESKD is approximately 45 years of age, although this varies widely from 20 to over 70 years of age, even among family members with the same mutation. The reason for this variation in age of ESKD is unclear. | mucin 1, cell surface associated | ||||
| 288 | Mucopolysaccharidosis type 7 | GUSB | A rare, genetic lysosomal storage disease characterized by accumulation of glycosaminoglycans in connective tissue which results in progressive multisystem involvement with severity ranging from mild to severe. The most consistent features include musculoskeletal involvement (particularly dysostosis multiplex, joint restriction, thorax abnormalities, and short stature), limited vocabulary, intellectual disability, coarse facies with a short neck, pulmonary involvement (predominantly decreased pulmonary function), corneal clouding, and cardiac valve disease. | glucuronidase beta | ||||
| 289 | Multicentric osteolysis, nodulosis, and arthropath | MMP2 | Multicentric osteolysis nodulosis and arthropathy spectrum is a group of rare congenital skeletal disorders characterized by progressive bone loss, joint disease and bumps under the skin. People with these conditions have a loss of bone tissue, especially in the hands and feet; pain, swelling, stiffness and loss of motion in joints located in the hands, feet, knees, wrists, ankles and elbows; and firm, round bumps under the skin of the palms and soles. Other signs and symptoms include coarse facial features, skin abnormalities and heart defects. These conditions are caused by changes (variants) in the MMP2 gene or MMP14 gene that are typically inherited in a recessive pattern. Treatment is supportive and can include physical therapy, pain management and mobility aids. | matrix metallopeptidase 2 | ||||
| 290 | Multiple congenital anomalies-hypotonia-seizures syndrome type 2 | PIGA | A rare, genetic, lethal, neurometabolic malformation syndrome characterized by multiple, variable, congenital cardiac (systolic murmur, atrial septal defect), urinary (duplicated collecting system, vesicoureteral reflux) and central nervous system (thin corpus callosum, cerebellar hypoplasia) malformations associated with neonatal hypotonia, early-onset epileptic encephalopathy, and myoclonic seizures. Craniofacial dysmorphism (prominent occiput, enlarged fontanel, fused metopic suture, upslanted palpebral fissures, overfolded helix, depressed nasal bridge, anteverted nose, malar flattening, microstomy with downturned corners, Pierre-Robin sequence, high arched palate, short neck) and other manifestations (joint contractures, hyperreflexia, dysplastic nails, developmental delay) are also observed. | phosphatidylinositol glycan anchor biosynthesis class A | ||||
| 291 | Multiple endocrine neoplasia type 2A | RET | Multiple endocrine neoplasia, type 2A (MEN 2A) is an autosomal dominant syndrome characterized by medullary carcinoma of the thyroid, pheochromocytoma, parathyroid hyperplasia or adenomas (causing hyperparathyroidism), and occasionally cutaneous lichen amyloidosis. Clinical features depend on the glandular elements affected. Familial medullary thyroid carcinoma is a distinct variant of MEN 2A. Diagnosis is confirmed by genetic testing. Hormonal and imaging tests help locate the tumors, which are removed surgically when possible. | ret proto-oncogene | ||||
| 292 | Multiple endocrine neoplasia type 2B | RET | Multiple endocrine neoplasia, type 2B (MEN 2B) is an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas and intestinal ganglioneuromas, and often a marfanoid habitus and other skeletal abnormalities. Symptoms depend on the glandular abnormalities present. Diagnosis is confirmed by genetic testing. Hormonal and imaging tests help locate the tumors, which are removed surgically when possible. | ret proto-oncogene | ||||
| 293 | Multiple self-healing squamous epithelioma | Prevalence is unknown but over 100 cases have been reported worldwide | TGFBR1 | No aliases | Multiple self-healing squamous epithelioma (also known as Ferguson-Smith disease or TGFB1 mutation syndrome) is a rare genetic disorder characterized by the development of multiple skin tumors that tend to heal spontaneously. It is caused by mutations in the TGFB1 gene, which is involved in regulating cell growth and division. Individuals with this condition typically develop noncancerous tumors on their skin, particularly on sun-exposed areas. The tumors often recur but have a tendency to resolve on their own without treatment, hence the term self-healing. | transforming growth factor beta receptor 1 | ||
| 294 | Multiple sulfatase deficiency | 1 per million individuals worldwide | SUMF1 | Sulfatase Modifying Factor 1 , FGE 2 , UNQ3037 , C-Alpha-Formylglycine-Generating Enzyme 1 | Multiple sulfatase deficiency (MSD) is a rare genetic disorder characterized by the impaired activity of multiple sulfatase enzymes in the body. These enzymes are crucial for breaking down certain molecules, leading to the accumulation of sulfatides and other substances in tissues and organs. Symptoms typically appear in infancy and include developmental delay, neurological problems, skeletal abnormalities, and organ dysfunction. MSD is caused by mutations in the SUMF1 gene, which plays a role in activating sulfatase enzymes | sulfatase modifying factor 1 | ||
| 294 | Multiple self-healing squamous epithelioma | Prevalence is unknown but over 100 cases have been reported worldwide | TGFBR1 | No aliases | Multiple self-healing squamous epithelioma (also known as Ferguson-Smith disease or TGFB1 mutation syndrome) is a rare genetic disorder characterized by the development of multiple skin tumors that tend to heal spontaneously. It is caused by mutations in the TGFB1 gene, which is involved in regulating cell growth and division. Individuals with this condition typically develop noncancerous tumors on their skin, particularly on sun-exposed areas. The tumors often recur but have a tendency to resolve on their own without treatment, hence the term self-healing. | transforming growth factor beta receptor 1 | ||
| 295 | Myhre syndrome | unknown | SMAD4 | DPC4 (Deleted in Pancreatic Cancer 4), MADH4 (Mothers Against Decapentaplegic Homolog 4), JV18-1 | Myhre syndrome is a rare genetic disorder characterized by distinctive facial features, short stature, stiff joints, and thickened skin. Individuals with this syndrome may also experience developmental delays, hearing loss, heart defects, and respiratory issues. Myhre syndrome is caused by mutations in the SMAD4 gene, which affects the regulation of cellular processes. The condition is typically diagnosed based on clinical features and genetic testing. Treatment is symptomatic and supportive, addressing the specific needs and complications of each individual. | SMAD family member 4 | ||
| 296 | Naegeli-Franceschetti-Jadassohn syndrome | SCO2 | Myopia (nearsightedness) is a common condition that’s usually diagnosed before age 20. It affects your distance vision — you can see objects that are near, but you have trouble viewing objects that are farther away like grocery store aisle markers or road signs. Myopia treatments include glasses, contact lenses or surgery. | synthesis of cytochrome C oxidase 2 | ||||
| 297 | Naegeli-Franceschetti-Jadassohn syndrome | 1 case in 2-4 million population | KRT14 | Keratin-14 (K14), Cytokeratin-14 (CK14), Cytokeratin-14 (KRT14), Keratin type I cytoskeletal 14, Epidermolysis bullosa simplex, Dowling-Meara type (EBS3), | Naegeli-Franceschetti-Jadassohn syndrome (NFJS) is a rare genetic disorder that affects the skin, teeth, and nails. It is caused by mutations in the KRT14 gene, which encodes keratin 14, a protein essential for the structural integrity of skin cells. Symptoms of NFJS typically include a reticulated pattern of skin pigmentation, thickened palms and soles, dental anomalies, nail dystrophy, and a lack of dermatoglyphics (fingerprints). The condition is inherited in an autosomal dominant pattern. Diagnosis is based on clinical features and confirmed through genetic testing. | keratin 14 | ||
| 298 | Nail-patella syndrome | approximately 1 in 50,000 individuals | LMX1B | LIM homeobox transcription factor 1 beta, LMX1.2, LIM/homeobox protein LMX1.2, LMX1.1 | Nail-Patella Syndrome (NPS) is a genetic disorder characterized by abnormalities of the nails, knees, elbows, and pelvis. It is caused by mutations in the LMX1B gene. Key features include nail dysplasia, patellar hypoplasia or aplasia, elbow contractures, and iliac horns. The condition can also be associated with kidney disease and glaucoma. NPS is inherited in an autosomal dominant pattern. | LIM homeobox transcription factor 1 beta | ||
| 299 | Nail-patella-like renal disease | 1/50,000 | LMX1B | LIM homeobox transcription factor 1 beta, LMX1.2, LIM/homeobox protein LMX1.2, LMX1.1 | Nail-Patella Syndrome (NPS) is a genetic disorder characterized by abnormalities of the nails, knees, elbows, and pelvis. It is caused by mutations in the LMX1B gene. Key features include nail dysplasia, patellar hypoplasia or aplasia, elbow contractures, and iliac horns. The condition can also be associated with kidney disease and glaucoma. NPS is inherited in an autosomal dominant pattern. | LIM homeobox transcription factor 1 beta | ||
| 300 | Nance-Horan syndrome | NHS | Nasopharyngeal carcinoma (NPC) is a type of cancer that originates in the nasopharynx, the upper part of the throat behind the nose. It is distinct from other head and neck cancers due to its association with Epstein-Barr virus (EBV) infection and specific environmental and genetic factors. NPC is more common in certain populations, particularly in Southeast Asia and Southern China. Symptoms may include a persistent lump in the neck, nasal congestion, blood-tinged saliva, hearing loss, and headaches. RAB3GAP1 (RAB3 GTPase-activating protein catalytic subunit) is not directly associated with Nasopharyngeal Carcinoma (NPC). It is primarily involved in cellular processes such as intracellular protein trafficking and synaptic vesicle exocytosis. Therefore, there isn't a relevant description connecting RAB3GAP1 with Nasopharyngeal Carcinoma. | NFKB inhibitor alpha | ||||
| 301 | Nasopharyngeal carcinom | NFKBIA | Nasopharyngeal carcinoma (NPC) is a type of cancer that originates in the nasopharynx, the upper part of the throat behind the nose. It is distinct from other head and neck cancers due to its association with Epstein-Barr virus (EBV) infection and specific environmental and genetic factors. NPC is more common in certain populations, particularly in Southeast Asia and Southern China. Symptoms may include a persistent lump in the neck, nasal congestion, blood-tinged saliva, hearing loss, and headaches. RAB3GAP1 (RAB3 GTPase-activating protein catalytic subunit) is not directly associated with Nasopharyngeal Carcinoma (NPC). It is primarily involved in cellular processes such as intracellular protein trafficking and synaptic vesicle exocytosis. Therefore, there isn't a relevant description connecting RAB3GAP1 with Nasopharyngeal Carcinoma. | NFKB inhibitor alpha | ||||
| 302 | Navajo neurohepatopathy | unknown | MPV17L | MPV17-like protein, MPV17-related protein, Mpv17-like protein | Navajo neurohepatopathy (NNH) is a rare genetic disorder primarily affecting the Navajo population. It is characterized by neurological symptoms such as developmental delay, seizures, and movement disorders, along with liver dysfunction including hepatomegaly and liver fibrosis.Navajo neurohepatopathy is a severe neurological and hepatic disorder primarily affecting Navajo children. It is caused by mutations in the MPV17L gene, also known as MPV17-like protein, which plays a crucial role in mitochondrial function. This condition leads to progressive neurological deterioration, liver dysfunction, and often results in early childhood death. Symptoms typically include developmental delay, seizures, liver failure, and progressive neurologic decline. | mitochondrial inner membrane protein MPV17 | ||
| 303 | Neonatal ichthyosis-sclerosing cholangitis syndrome | CLDN1 | Neonatal ichthyosis-sclerosing cholangitis (NISCH syndrome) is a very rare complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis.The ichthyosis presents with diffuse white scales sparing the skin folds, and is accompanied by scalp hypotrichosis, cicatricial alopecia, and sparse eyelashes/eyebrows. Additional manifestations may include oligodontia, hypodontia and enamel dysplasia. All patients present with neonatal sclerosing cholangitis with jaundice and pruritus, hepatomegaly, and biochemical cholestasis. Overall, the clinical picture mimics biliary atresia (see this term). Portal hypertension, patent extrahepatic bile duct obstruction and splenomegaly may also be present. Histology shows extensive fibrosis and bile duct proliferation. Leukocyte vacuolization is a common finding. The hepatic disease may have variable expressivity, ranging from a progressive disease resulting in liver failure to regression of cholestasis. | claudin 1 | ||||
| 304 | Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features | CHAMP1 | Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features (NEDHILD) is a rare neurodevelopmental disorder associated with impaired intellectual development, speech and language impairment, microcephaly, seizures, hypotonia, ophthalmologic issues, constipation/gastroesophageal reflux, and behavioral problems, including autism and sleep disturbances . | chromosome alignment maintaining phosphoprotein 1 | ||||
| 305 | Neurofibromatosis type 2 | NF2 | Neurofibromatosis type 2 is a disorder characterized by the growth of noncancerous tumors in the nervous system. The most common tumors associated with neurofibromatosis type 2 are called vestibular schwannomas. These growths develop along the nerve that carries information from the inner ear to the brain (the auditory nerve). Tumors that form on the membrane that covers the brain and spinal cord (meninges) are also common in neurofibromatosis type 2. These tumors are called meningiomas. Tumors can also occur on other nerves or tissues in the brain or spinal cord in people with this condition. | NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor | ||||
| 306 | Neurogenic arthrogryposis multiplex congenita | ERGIC1 | Arthrogryposis is a general or descriptive term for the development of nonprogressive contractures affecting one or more areas of the body prior to birth (congenitally). A contracture is a condition in which a joint becomes permanently fixed in a bent (flexed) or straightened (extended) position, completely or partially restricting the movement of the affected joint. When congenital contractures occur only in one body area, it is not referred to as arthrogryposis but rather an isolated congenital contracture. The most common form of an isolated congenital contracture is clubfoot. | endoplasmic reticulum-golgi intermediate compartment 1 | ||||
| 307 | Nicolaides-Baraitser syndrome | SMARCA2 | Nicolaides-Baraitser syndrome (NCBRS) is characterized by sparse scalp hair, prominence of the inter-phalangeal joints and distal phalanges due to decreased subcutaneous fat, characteristic coarse facial features, microcephaly, seizures, and developmental delay / intellectual disability. Seizures are of various types and can be difficult to manage. Developmental delay / intellectual disability (ID) is severe in nearly a half, moderate in a third, and mild in the remainder. Nearly a third never develop speech or language skills. | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 | ||||
| 308 | Obesity due to congenital leptin deficiency | LEP | Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia.Patients with congenital leptin deficiency are severely hyperphagic from early infancy and, although birthweight is normal, they rapidly become obese during early childhood. An increased susceptibility to infections has also been reported in these infants and appears to be associated with reduced numbers of circulating CD4+ T cells, and impaired T cell proliferation and cytokine release. Other features of the disorder include hyperinsulinaemia, advanced bone age, hypothalamic hypothyroidism and hypogonadotropic hypogonadism leading to a failure to undergo puberty. | leptin | ||||
| 309 | Oculocerebrofacial syndrome, Kaufman type | UBE3B | A rare, genetic, syndromic intellectual disability characterized by severe intellectual disability, distinctive craniofacial features and variable multiple congenital anomalies including ocular, brain, urogenital and skeletal abnormalities.he most prominent clinical findings are severe intellectual disability, pre-and postnatal growth retardation, microcephaly, and typical craniofacial features which include non-progressive microcephaly of prenatal onset, prominence of the zygomatic region of the face, full cheeks, prominent frontal tubers, sparse and arched eyebrows, blepharophimosis with epicanthal folds, upslanted palpebral fissures, preauricular skin tags, underdeveloped and abnormally folded ears, wide nasal base, low nasal bridge, anteverted nares, long and flat philtrum and retrognathia. Hypotonia, feeding difficulties, failure to thrive and poor speech development are universal findings. | ubiquitin protein ligase E3B | ||||
| 310 | Oculocutaneous albinism type 1B | TYR | Oculocutaneous albinism is a group of conditions that affect coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have very fair skin and white or light-colored hair. Long-term sun exposure greatly increases the risk of skin damage and skin cancers, including an aggressive form of skin cancer called melanoma, in people with this condition. Oculocutaneous albinism also reduces pigmentation of the colored part of the eye (the iris) and the light-sensitive tissue at the back of the eye (the retina). People with this condition usually have vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); and increased sensitivity to light (photophobia). | tyrosinase | ||||
| 311 | Oculocutaneous albinism type 3 | TYRP1 | A form of oculocutaneous albinism (OCA) characterized by rufous or brown albinism and occurring mainly in the African population.Visual anomalies, such as nystagmus, are frequently undetectable and patients usually present with one of two phenotypes: rufous OCA (ROCA), characterized by red-bronze skin color, blue or brown irises and ginger-red hair, or brown OCA (BOCA), characterized by light to brown hair and a light to brown or tan skin color. The clinical features of OCA3 have been considered as rather mild, and in the rare cases of non-African patients, reddish hair color has been reported. A Japanese girl was reported with having OCA3 who presented with blond hair and light skin (with a small Mongolian spot), was able to tan and was negative for nystagmus | tyrosinase related protein 1 | ||||
| 312 | Odonto-onycho-dermal dysplasi | WNT10A | A rare, genetic, ectodermal dysplasia syndrome characterized by dental abnormalities (primarily agenesis of the permanent and deciduous teeth with cone-shaped incisors and canines), onychodysplasia, palmoplantar hyperkeratosis, dry skin and, more variably, hypotrichosis, and sweat gland dysfunction (hyper- or hypohidrosis). | Wnt family member 10A | ||||
| 313 | Ornithine transcarbamylase deficiency | The estimated prevalence of OTCD is in the range of 1 in 14,000 to 1 in 80,000 | OTC | OTCase OTCD OTC1 Ornithine Carbamoyltransferase, Mitochondrial Ornithine Transcarbamylase, Mitochondrial Ornithine Transcarbamylase Deficiency Ornithine Carbamoyltransferase OCTD | Ornithine transcarbamylase deficiency (OTCD) is the most prevalent genetic disorder within urea cycle disorders, characterized by X-linked inheritance and variable phenotypic expression. Homozygous males with severe neonatal onset present shortly after birth with hyperammonemia, while late-onset cases may display mild neurocognitive symptoms. The severity of OTCD ranges from potentially lethal to enduring neurocognitive deficits. OTCD is caused by mutations in the OTC gene, leading to a deficiency of the enzyme ornithine transcarbamylase. This enzyme is crucial for converting ammonia into urea, which can then be excreted from the body. | ornithine transcarbamylase | ||
| 314 | Orofaciodigital syndrome type 2 | prevalence of fewer than 1 in 200,000 individuals | NEK1 | NY-REN-55 NIMA (Never In Mitosis Gene A)-Related Kinase Serine/Threonine-Protein Kinase Nek Never In Mitosis A-Related Kinase Renal Carcinoma Antigen NY-REN-55 NimA-Related Protein Kinase Protein-Serine/Threonine Kinase 3 | Oral-facial-digital syndrome (OFDS) is a group of conditions that affect the development of their oral cavity (mouth, tongue, teeth, and jaw), face (head, eyes and nose) and finger and toes (digits). Common signs and symptoms include a split (cleft) in the lip and a tongue with an unusual lobed shape. There may also be growth of noncancerous tumors or nodules on the tongue. Affected people may have extra, missing, or differently shaped teeth. Another common feature is an opening in the roof of the mouth (cleft palate). Some people with OFDS have bands of extra tissue (gingival frenula) that attach the lip to the gums. Distinct facial features include a wide nose with a broad, flat nasal bridge and widely spaced eyes (hypertelorism). Fusion of certain digits (syndactyly), short digits (brachydactyly), curved digits (clinodactyly) or extra fingers/toes (polydactyly) are commonly seen in OFDS. People with OFDS also have issues with the development and structure of the brain. Mild to severe intellectual disability is seen in affected people. | NIMA related kinase 1 | ||
| 315 | Osteocraniostenosis | FAM111A | Osteocraniostenosis is a lethal skeletal dysplasia characterized by a cloverleaf skull anomaly, facial dysmorphism, limb shortness, splenic hypo/aplasia and radiological anomalies including thin tubular bones with flared metaphyses and deficient calvarial mineralization.This multiple congenital anomalies syndrome is characterized by dysmorphic features of the fetus and the newborn: the skull is misshapen, combining acrocephaly and cloverleaf deformity, fontanelles are very large; facial dysmorphism includes midface hypoplasia with telecanthus, short upturned nose, short philtrum, small inverted V-shaped mouth and low-set ears; limbs are also affected with bowed forearms, micromelia and acromicria with brachydactyly.' | FAM111 trypsin like peptidase A | ||||
| 316 | Osteofibrous dysplasia | MET | Osteofibrous Dysplasia is a rare benign tumor-like condition that primarily affects the cortices of the tibia. The condition typically presents in patients less than 10 years of age with painless anterior shin swelling. Diagnosis is made by a combination of radiographs showing an anterior eccentric lytic tibial lesion and biopsy showing fibroblast proliferation surrounding islands of woven bone with osteoblastic rimming. Treatment is usually observation alone as lesions usually regress and do not cause problems in adulthood. | MET proto-oncogene, receptor tyrosine kinas | ||||
| 317 | Osteogenesis imperfecta, type viii | 1 in 10,000 to 20,000 people worldwide. | P3H1 | LEPRE1 (Leprecan 1) GROS1 Osteogenesis Imperfecta Type VIII (OI8) Leucine- And Proline-Enriched Proteoglycan Procollagen-Proline 3-Dioxygenase | Type VIII OI, a rare autosomal-recessive disorder characterised by white sclerae, severe growth deficiency and bone fragility, was added to the classification in 2007 as a severe and lethal type. OI Type VIII is caused by mutations in the genes P3H1 or CRTAP. These genes are involved in collagen formation, particularly in modifying the protein necessary for the development of strong bonesd. | prolyl 3- hydroxylase 1 | ||
| 318 | Osteopathia striata-cranial sclerosis syndrome | approximately 0.1/1 million people | AMER1 | WTX FAM123B Adenomatous Polyposis Coli Membrane Recruitment Wilms Tumor Gene On The X Chromosome Protein Family With Sequence Similarity 123B Wilms Tumor On The X Protein FAM123B Amer1 OSCS | Osteopathia striata with cranial sclerosis (OSCS), also known as Voorhoeve disease, is a rare genetic disorder characterized by distinctive bone abnormalities. It involves a combination of longitudinal striations seen on the long bones and sclerosis (abnormal hardening) of the cranial bones.Approximately half have associated features including orofacial clefting and hearing loss, and a minority have some degree of developmental delay (usually mild). Typically inherited in an X-linked dominant manner. Mutations in the AMER1 gene (also known as WTX) have been associated with OSCS. | APC membrane recruitment protein 1 | ||
| 319 | Osteopetrosis with renal tubular acidosis | CA2 | Osteopetrosis with renal tubular acidosis is a rare disorder characterized by osteopetrosis (see this term), renal tubular acidosis (RTA), and neurological disorders related to cerebral calcifications. Patients present a triad of mild osteopetrosis, mixed proximal and distal RTA, and intracerebral calcifications. Other clinical manifestations include fractures, growth failure and short stature, developmental delay, intellectual deficit, dental malocclusions/malalignment, cranial nerve compression and hearing impairment. | carbonic anhydrase 2 | ||||
| 320 | Osteopetrosis, autosomal recessive 1 | an incidence of 1:250,000 live births | TCIRG1 | ATP6i Atp6v0a3 OC116 TIRC7 V-ATPase 116 kDa isoform a3 | Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Patients suffer severe symptoms, including growth retardation, skull abnormalities (macrocephaly, frontal bossing, choanal stenosis), hydrocephalus, hypocalcemia (owing to the defective calcium mobilization activity of osteoclasts) and abnormal tooth eruption. The abnormal bone density causes an expansion of skeletal tissue into marrow cavities at the expense of the bone marrow niche, leading to severe anemia, bleeding, frequent infections and hepatosplenomegaly due to increased extramedullary hematopoiesis. More than 50% of ARO cases are caused by mutations in the T cell immune regulator 1 (TCIRG1) gene, which encodes the V-type proton ATPase 116 kDa subunit a3 (OC116). It acidifies the bone resorption lacunae, favoring the dissolution of hydroxyapatite crystals, which form the bone mineral fraction, and the degradation of the organic bone matrix. | T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 | ||
| 321 | Osteopetrosis, autosomal recessive 5 | OSTM1 | Autosomal recessive osteopetrosis-5 is a form of infantile malignant osteopetrosis, characterized by defective osteoclast function resulting in decreased bone resorption and generalized osteosclerosis. Defective resorption causes development of densely sclerotic fragile bones and progressive obliteration of the marrow spaces and cranial foramina. Marrow obliteration is associated with extramedullary hematopoiesis and hepatosplenomegaly, and results in anemia and thrombocytopenia, whereas nerve entrapment accounts for progressive blindness and hearing loss. | osteoclastogenesis associated transmembrane protein 1 | ||||
| 322 | Osteoporosis-pseudoglioma syndrome | approximately 0.5–1 per 1,000,000. | LRP5 | LR3 BMND1 (Bone mineral density 1) EVR1 (Endosteal vascularization receptor 1) HBM (High bone mass) OPPG (Osteoporosis-pseudoglioma syndrome) VBCH2 EVR4 LRP7 | Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal-recessive disorder, characterized by severe osteoporosis and early-onset blindness. Loss of function mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) which plays a crucial role in the regulation of bone density and eye development have been established as the genetic defect of the disease. In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes).Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye.seudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma. | LDL receptor related protein 5 | ||
| 323 | Overhydrated hereditary stomatocytosis | RHAG | RH50 Rh50A RHG SLC42A1 (Solute carrier family 42 member 1) | Overhydrated hereditary stomatocytosis (OHSt), which is clinically characterized by a hemolytic anemia, is a rare disorder of red blood cells (RBCs) associated with increased membrane permeability to monovalent cations and increased activity of the Na+K+-ATPase. OHSt is associated with mutations in the gene encoding the Rh-associated glycoprotein (RhAG), a member of the Rh complex.RhAG may function as an ammonium transporter and/or a gas channel.Clinical symptoms may include Hemolytic anemia: Due to the increased fragility and destruction of red blood cells, patients may present with symptoms of anemia, such as fatigue, pallor, and jaundice. Splenomegaly: Enlargement of the spleen due to increased breakdown of abnormal red blood cells. Stomatocytes: Presence of stomatocytes on blood smear, a key diagnostic feature. Edema: Generalized swelling due to fluid retention in the body, though this is less common. Gallstones: Due to chronic hemolysis, patients may develop gallstones. | Rh associated glycoprotein | |||
| 324 | Oxoglutaric aciduria | OGDH | OGDC (Oxoglutarate Dehydrogenase Complex) OGDC-E1 (Oxoglutarate Dehydrogenase Complex, E1 Component) KGD (Ketoglutarate Dehydrogenase) OGD (Oxoglutarate Dehydrogenase) alpha-KGDH (Alpha-Ketoglutarate Dehydrogenase) | Oxoglutaric aciduria, also known as alpha-ketoglutaric aciduria, is a rare metabolic disorder characterized by the abnormal accumulation of oxoglutaric acid (alpha-ketoglutarate) in the urine. This condition results from a defect in the metabolic pathways involving the tricarboxylic acid (TCA) cycle or the glutamine/glutamate metabolism.It is usually inherited in an autosomal recessive manner,The clinical presentation of oxoglutaric aciduria can vary widely but may include: Developmental Delay: Delays in reaching developmental milestones. Hypotonia: Low muscle tone, which can affect motor skills. Metabolic Acidosis: An increased acid level in the body, leading to symptoms such as rapid breathing, fatigue, and confusion. Neurological Symptoms: Seizures, intellectual disability, and other neurological impairments. Growth Retardation: Poor growth and physical development. | oxoglutarate dehydrogenasen | |||
| 325 | Pallister-Hall syndrome | UNKNOWN | GLI3 | ACLS. GCPS. GLI-Kruppel family member GLI3 (Greig cephalopolysyndactyly syndrome) GLI3_HUMAN. oncogene GLI3. PAP-A. PAPA. PAPA1. | GLI3-related Pallister-Hall syndrome (GLI3-PHS) is characterized by a spectrum of anomalies ranging from polydactyly, asymptomatic bifid epiglottis, and hypothalamic hamartoma at the mild end to laryngotracheal cleft with neonatal lethality at the severe end. Individuals with GLI3-PHS can have pituitary insufficiency and may die as neonates from undiagnosed and untreated adrenal insufficiency. Pallister-Hall syndrome is caused by mutations in the GLI3 gene, which plays a critical role in the development of various body parts. It is inherited in an autosomal dominant pattern, | GLI family zinc finger 3 | ||
| 326 | Palmoplantar keratoderma i, striate, focal, or diffuse | DSG1 | Desmoglein CDHF4 Pemphigus Foliaceus Antigen Desmosomal Glycoprotein Cadherin Family Member Desmoglein-1 | Hereditary palmoplantar keratodermas (PPK) are a heterogeneous group of keratinizing disorders characterized by hyperkeratotic thickening of the palms and soles.The mutations in the genes encoding proteins involved in keratinization process, such as keratins, desmosomes, loricrin, cathepsin C, gap junction proteins, and many others have been implicated in pathogenesis of PPK. Symptoms include in different types: Striate Palmoplantar Keratoderma Linear Streaks, Hyperkeratosis, Pain and Discomfort Focal Palmoplantar Keratoderma Localized Thickening , Callus-like Lesions, Pain Diffuse Palmoplantar Keratoderma Uniform Hyperkeratosis, Yellowish or Brownish Color, Extension Beyond Palms and Soles, Pain and Cracking. The DSG1 gene (Desmoglein 1) encodes a protein that is a member of the desmoglein subfamily of desmosomal cadherins. Desmosomes are specialized structures within the cell membrane that help to anchor cells together, providing mechanical strength to tissues that undergo significant stress, such as the skin. | desmoglein 1 | |||
| 327 | Papilloma of choroid plexus | average annual incidence of choroid plexus tumors is 0.3/100,000 | TP53 | P53 LFS1 Cellular Tumor Antigen P53 Phosphoprotein P53 Antigen NY-CO-13 Transformation-Related Protein 53 Mutant Tumor Protein 53 Li-Fraumeni Syndrome Tumor Suppressor P53 Tumor Supressor P53 | Choroid plexus papillomas are benign tumors that typically occur in the supratentorial compartment in children and the infratentorial compartment in adults. The typical clinical presentation is one of hydrocephalus or increased intracranial pressure. Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction. Headaches: Persistent or severe headaches due to elevated ICP. Nausea and Vomiting: Often associated with increased ICP. Hydrocephalus: Accumulation of excess fluid in the brain ventricles, which can cause swelling. Visual Disturbances: Such as double vision or loss of vision. Balance and Coordination Problems: Due to pressure on the cerebellum or brainstem. Irritability and Lethargy: Particularly in young children. Developmental Delays: In infants and young children due to pressure effects on developing brain structures. These tumors are usually benign and associated with specific genetic mutations, including alterations in the TP53 gene. | tumor protein p53 | ||
| 328 | Parkinson disease 2, autosomal recessive juvenile | PRKN | Parkin AR-JP PARK2 PDJ Parkinson Juvenile Disease Protein E3 Ubiquitin-Protein Ligase Parkin Parkinson Protein 2 E3 Ubiquitin Protein Ligase Parkin RBR E3 Ubiquitin-Protein Ligase Parkinson Disease Protein E3 Ubiquitin Ligase | Parkinson's disease 2 (PD2) refers to a specific subtype of Parkinson's disease (PD) that manifests in early childhood or adolescence.It is inherited in an autosomal recessive pattern,Mutations in the PRKN gene are primarily responsible for PD2. PRKN encodes for a protein called parkin, which plays a crucial role in protein degradation and mitochondrial function within cells.Symptoms include tremor, dystonia,rigidity, postural instability, bradykinesia, gait disturbances neuronal loss and gliosis in the substantia nigra pars compacta parkinsonism, early-onset hyperreflexia may occur diurnal fluctuations of symptoms (in a subset of patients) neuronal loss in the locus ceruleus. | parkin RBR E3 ubiquitin protein ligase | |||
| 329 | Paroxysmal nocturnal hemoglobinuria | occurrence estimated as high as 15.9 individuals per million worldwide | PIGA | Class A GlcNAc-Inositol Phospholipid Assembly Protein GPI3 (SPT14) Homolog (S. Cerevisiae) Paroxysmal Nocturnal Hemoglobinuria GLCNAC-PI Synthesis Protein GlcNAc-PI Synthesis Protein GPI Anchor Biosynthesis MCAHS2 | Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease that presents clinically with a variety of symptoms, the most prevalent of which are hemolytic anemia, hemoglobinuria, and somatic symptoms including fatigue and shortness of breath. Other findings associated with PNH include thrombosis, renal insufficiency, and in the later course of the disease, even bone marrow failure. The condition is genetic, with the mutations occurring on the X linked gene.Paroxysmal nocturnal hemoglobinuria occurs due to the development of a genetic mutation in hematopoietic stem cells. This mutation of the X-linked gene phosphatidylinositol glycan class A (PIGA), produces a deficiency in the glycosylphosphatidylinositol (GPI) protein, which is responsible for anchoring other protein moieties to the surface of erythrocytes. | phosphatidylinositol glycan anchor biosynthesis class A | ||
| 330 | Partial androgen insensitivity syndrome | AR | Partial androgen insensitivity syndrome (PAIS) is genetic condition that affects the sexual development of a male fetus. During pregnancy, male fetuses with PAIS are unable to properly respond to male sex hormones (androgens). As a result, this affects the development of the genitals. The appearance of the genitals may vary from person to person. Some males have an unusually small penis (microphallus), undescended testes, hypospadias (urethra located on the underside of the penis), and/ or bifid scrotum (scrotum split in two). | androgen receptor | ||||
| 331 | Peutz-Jeghers syndrome | estimated prevalence of 1:8000 to 1:200,000 births | STK11 | LKB1 PJS Serine/Threonine-Protein Kinase STK11 Polarization-Related Protein LKB1 Renal Carcinoma Antigen NY-REN-19 Liver Kinase B1 HLKB1 Serine/Threonine Kinase 11 (Peutz-Jeghers Syndrome) Serine/Threonine-Protein Kinase LKB1 Serine/Threonine-Protein Kinase 11 | Peutz-Jeghers syndrome (PJS) is characterized by the association of gastrointestinal (GI) polyposis, mucocutaneous pigmentation, and cancer predisposition. PJS-type hamartomatous polyps are most common in the small intestine (in order of prevalence: jejunum, ileum, and duodenum) but can also occur in the stomach, large bowel, and extraintestinal sites including the renal pelvis, bronchus, gall bladder, nasal passages, urinary bladder, and ureters. GI polyps can result in chronic bleeding, anemia, and recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection. Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are common. The macules may fade in puberty and adulthood.Individuals with PJS are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers). Females are at risk for sex cord tumors with annular tubules (SCTAT), a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rare aggressive cancer. Males occasionally develop large calcifying Sertoli cell tumors of the testes, which secrete estrogen and can lead to gynecomastia, advanced skeletal age, and ultimately short stature, if untreated.PJS is inherited in an autosomal dominant manner.The STK11 gene provides instructions for making a protein that acts as a tumor suppressor, which helps control cell growth and division. | serine/threonine kinase 11 | ||
| 333 | PGM3-CDG | PGM3 | A rare congenital disorder of glycosylation caused by mutations in the PGM3 gene and characterized by neonatal to childhood onset of recurrent bacterial and viral infections, inflammatory skin diseases, atopic dermatitis and atopic diatheses, and marked serum IgE elevation. Early neurologic impairment is evident including developmental delay, intellectual disability, ataxia, dysarthria, sensorineural hearing loss, myoclonus and seizures. | phosphoglucomutase 3 | ||||
| 332 | PGM1-CDG | PGM1 | Glucose Phosphomutase Phosphoglucomutase-1 PGM CDG1T 3 | PGM1-CDG (Phosphoglucomutase 1 deficiency) is a type of Congenital Disorders of Glycosylation (CDG), specifically caused by mutations in the PGM1 gene. PGM1 (Phosphoglucomutase 1) gene encodes an enzyme called phosphoglucomutase 1, which plays a crucial role in glucose metabolism and the production of glucose-1-phosphate.PGM1-CDG is inherited in an autosomal recessive pattern.Common symptoms may include: Developmental Delay: Delayed motor skills and speech development. Muscle Weakness: Hypotonia (low muscle tone) and muscle weakness. Intellectual Disability: Ranging from mild to severe intellectual impairment. Failure to Thrive: Difficulty gaining weight and growing at a normal rate. Seizures: Epileptic seizures may occur in some cases. Dysmorphic Features: Facial features may appear unusual or dysmorphic. Organ Involvement: Heart defects, liver dysfunction, and gastrointestinal issues may be present in some individuals. Coagulation Disorders: Abnormal bleeding tendencies due to impaired glycosylation of clotting factors. | phosphoglucomutase 1 | |||
| 333 | PGM3-CDG | PGM3 | A rare congenital disorder of glycosylation caused by mutations in the PGM3 gene and characterized by neonatal to childhood onset of recurrent bacterial and viral infections, inflammatory skin diseases, atopic dermatitis and atopic diatheses, and marked serum IgE elevation. Early neurologic impairment is evident including developmental delay, intellectual disability, ataxia, dysarthria, sensorineural hearing loss, myoclonus and seizures. | phosphoglucomutase 3 | ||||
| 334 | Phosphoenolpyruvate carboxykinase deficiency, cytosolic | PCK1 | PEPCK deficiency is an extremely rare disorder characterized by episodes of low blood sugar (hypoglycemia). It is a disorder of carbohydrate metabolism caused by a deficiency in the enzyme called phosphoenolpyruvate carboxykinase or PEPCK. This enzyme normally converts proteins and fats to glucose during times of fasting, in a process called gluconeogenesis. The glucose is used as a source of energy by the body. PEPCK deficiency is inherited in an autosomal recessive pattern. | phosphoenolpyruvate carboxykinase 1 | ||||
| 335 | Pilomatrixoma | CTNNB1 | A pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a benign appendageal tumor with differentiation toward hair follicle matrix cells. It usually manifests as a solitary, asymptomatic, firm nodule. It has long been considered a rare tumor, but it may be more common than previously realized. It is more common in children, but occurrence in adults is increasingly being recognized. [1, 2, 3, 4, 5] Recommended treatment is surgical excision. Multiple pilomatrixomas have been observed, mainly in association with myotonic dystrophy, but also with other syndromes including Rubenstein-Taybi syndrome and constitutional mismatch repair deficiency (CMMRD) syndrome. [6, 7, 8] Pilomatrix carcinoma is a rare condition | catenin beta 1 | ||||
| 336 | Pitt-Hopkins syndrome | TCF4 | Pitt-Hopkins syndrome is a condition characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features. People with Pitt-Hopkins syndrome have moderate to severe intellectual disability. Most affected individuals have delayed development of mental and motor skills (psychomotor delay). They are delayed in learning to walk and developing fine motor skills such as picking up small items with their fingers. People with Pitt-Hopkins syndrome typically do not develop speech; some may learn to say a few words. Many affected individuals exhibit features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills. | transcription factor 4 | ||||
| 337 | PMM2-CDG | PMM2 | PMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia) is an inherited condition that affects many parts of the body. The type and severity of problems associated with PMM2-CDG vary widely among affected individuals, sometimes even among members of the same family. | phosphomannomutase 2 | ||||
| 338 | Polycystic kidney disease 4 with or without polycystic liver disease | PKHD1 | PKD4 is an autosomal recessive polycystic kidney disease (ARPKD) characterized by enlarged, echogenic kidneys with fusiform dilatation of the collecting ducts. Most patients progress to end-stage renal disease (ESRD), but at varying ages. Patients also have liver disease consisting of dilated biliary ducts, congenital hepatic fibrosis (CHF), and portal hypertension (Caroli disease). The most typical disease expression occurs in neonates and includes a history of oligohydramnios, massively enlarged kidneys, and the 'Potter' sequence with pulmonary hypoplasia that leads to respiratory insufficiency and perinatal death in approximately 30% of affected newborns. | PKHD1 ciliary IPT domain containing fibrocystin/polyductin | ||||
| 339 | Polysyndactyly | GLI3 | Polysyndactyly or PPD4 is a form of preaxial polydactyly of fingers (see this term), a limb malformation syndrome, characterized by the presence of a thumb showing the mildest degree of duplication, being broad, bifid or with radially deviated distal phalanx. Syndactyly of various degrees of third-and-fourth fingers is occasionally present.. | GLI family zinc finger 3 | ||||
| 340 | Posterior urethral valve | BNC2 | .Posterior urethral valves (PUV) are obstructive membranes that develop in the urethra (tube that drains urine from the bladder), close to the bladder. The valve can obstruct or block the outflow of urine through the urethra. When this occurs, the bladder, ureters and kidneys become progressively dilated, which can lead to damage. | basonuclin 2 | ||||
| 341 | Postural orthostatic tachycardia syndrome due to NET deficiency | SLC6A2 | A condition where a deficiency in neuroendocrine tumors leads to abnormal heart rate increases upon standing, causing dizziness and fainting. | solute carrier family 6 member 2 | ||||
| 342 | PPARG-related familial partial lipodystrophy | PPARG | A genetic disorder involving abnormal fat distribution, usually leading to fat loss in certain areas and accumulation in others | peroxisome proliferator activated receptor gamma | ||||
| 343 | Primary dystonia, DYT2 typ | HPCA | A movement disorder characterized by sustained muscle contractions and abnormal postures, caused by mutations in the TOR1A gene. | hippocalcin | ||||
| 344 | Primary familial polycythemia | EPOR | A blood disorder leading to elevated red blood cell levels without a secondary cause, increasing the risk of blood clots. | erythropoietin receptor | ||||
| 345 | Progressive encephalopathy with leukodystrophy due to DECR deficiency | NADK2 | A neurodegenerative disorder causing progressive brain damage and white matter abnormalities due to DECR enzyme deficiency. | NAD kinase 2, mitochondrial | ||||
| 346 | Progressive myoclonic epilepsy type 6 | GOSR2 | A form of epilepsy characterized by myoclonus (muscle jerks) and progressive neurological decline, associated with mutations in the SCARB2 gene. | golgi SNAP receptor complex member 2 | ||||
| 347 | Prune belly syndrome | CHRM3 | A congenital condition involving a triad of symptoms: absence of abdominal muscles, urinary tract abnormalities, and cryptorchidism in males. | cholinergic receptor muscarinic 3 | ||||
| 348 | Purine nucleoside phosphorylase deficiency | PNP | A genetic disorder that affects the breakdown of purine nucleosides, leading to immune system issues and neurological symptoms. | purine nucleoside phosphorylase | ||||
| 349 | Pyle disease | SFRP4 | A rare metabolic bone disorder characterized by osteopenia and increased bone fragility. | secreted frizzled related protein 4 | ||||
| 350 | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | PSTPIP1 | A syndrome combining severe infections, skin ulcerations, and acne, often associated with underlying immune dysfunction | proline-serine-threonine phosphatase interacting protein 1 | ||||
| 351 | Quebec platelet disorder | PLAU | A bleeding disorder caused by defective platelet function, leading to abnormal bleeding and bruising. | plasminogen activator, urokinase | ||||
| 352 | RAPADILINO syndrome | RECQL4 | A rare genetic disorder with features including short stature, developmental delay, and dysmorphic features. | RecQ like helicase 4 | ||||
| 353 | Reticular dysgenesis | AK2 | A severe immunodeficiency disorder resulting in the absence of immune cells, leading to severe infections and early mortality. | adenylate kinase 2 | ||||
| 354 | Reticular dysgenesis | AK2 | A severe immunodeficiency disorder resulting in the absence of immune cells, leading to severe infections and early mortality. | adenylate kinase 2 | ||||
| 355 | Retinal cone dystrophy 4 | CACNA2D4 | A rare retinal disorder affecting cone photoreceptor cells, leading to progressive vision loss. | calcium voltage-gated channel auxiliary subunit alpha2delta 4 | ||||
| 356 | Rippling muscle disease | CAV3 | A rare muscle disorder characterized by muscle rigidity and rippling, along with potential weakness and pain. | caveolin 3 | ||||
| 357 | Roberts syndrome | ESCO2 | A genetic disorder causing limb abnormalities, craniofacial dysmorphism, and growth retardation. | establishment of sister chromatid cohesion N-acetyltransferase 2 | ||||
| 358 | Rubinstein-Taybi syndrome due to 16p13.3 microdeletion | CREBBP | A condition associated with broad thumbs, toes, intellectual disability, and distinctive facial features due to a microdeletion on chromosome 16. | CREB binding protein | ||||
| 359 | Scalp-ear-nipple syndrome | KCTD1 | A rare genetic disorder characterized by abnormalities of the scalp, ears, and nipples. | potassium channel tetramerization domain containing 1 | ||||
| 360 | Scheie syndrome | IDUA | A type of mucopolysaccharidosis characterized by skeletal abnormalities, corneal clouding, and heart valve problems. | alpha-L-iduronidase | ||||
| 361 | Schilbach-Rott syndrome | PTCH1 | A genetic disorder with features including intellectual disability, facial dysmorphism, and growth retardation. | patched 1 | ||||
| 361 | Schilbach-Rott syndrome | PTCH1 | A genetic disorder with features including intellectual disability, facial dysmorphism, and growth retardation. | patched 1 | ||||
| 362 | Schinzel-Giedion syndrome | SETBP1 | A severe genetic disorder marked by craniofacial dysmorphism, developmental delay, and skeletal abnormalities. | SET binding protein 1 | ||||
| 363 | Schwartz-Jampel syndrome | HSPG2 | A rare genetic disorder characterized by muscle stiffness, joint deformities, and growth retardation. | heparan sulfate proteoglycan 2 | ||||
| 364 | Self-improving dystrophic epidermolysis bullosa | COL7A1 | A form of epidermolysis bullosa with severe skin blistering that improves with age but may cause scarring and other complications. | collagen type VII alpha 1 chain | ||||
| 365 | Severe combined immunodeficiency due to adenosine deaminase deficiency | ADA | A critical immune disorder caused by adenosine deaminase deficiency, leading to severe susceptibility to infections. | adenosine deaminase | ||||
| 366 | Severe combined immunodeficiency due to FOXN1 deficiency | FOXN1 | A type of SCID caused by mutations in the FOXN1 gene, resulting in thymic and hair follicle abnormalities. | forkhead box N1 | ||||
| 367 | Severe intellectual disability-progressive spastic diplegia syndrome | CTNNB1 | A disorder characterized by severe intellectual disability and progressive muscle stiffness and weakness in the legs. | catenin beta 1 | ||||
| 368 | Short stature-pituitary and cerebellar defects-small sella turcica syndrome | LHX4 | A condition marked by short stature, pituitary gland dysfunction, cerebellar defects, and a small sella turcica. | LIM homeobox 4 | ||||
| 369 | SHORT syndrome | PIK3R1 | A genetic disorder characterized by short stature, heart defects, eye problems, and skeletal abnormalities. | phosphoinositide-3-kinase regulatory subunit 1 | ||||
| 370 | Sickle cell anemia | HBB | A genetic blood disorder causing red blood cells to become rigid and shaped like a sickle, leading to anemia, pain, and organ damage. | hemoglobin subunit beta | ||||
| 371 | Sickle cell-beta-thalassemia disease syndrome | HBB | A combination of sickle cell disease and beta-thalassemia, leading to severe anemia and related complications | hemoglobin subunit beta | ||||
| 372 | Sickle cell-hemoglobin C disease syndrome | HBB | A genetic condition where sickle cell disease and hemoglobin C disease coexist, causing anemia and other health issues. | hemoglobin subunit beta | ||||
| 373 | Sickle cell-hemoglobin D disease syndrome | HBB | A disorder involving the combination of sickle cell disease and hemoglobin D, leading to anemia and related complications. | hemoglobin subunit beta | ||||
| 374 | Singleton-Merten dysplasia | HBB | A rare genetic disorder with features including skeletal abnormalities, dental issues, and cardiac problems. | interferon induced with helicase C domain 1 | ||||
| 375 | Skin fragility-woolly hair-palmoplantar keratoderma syndrome | DSP | A rare condition characterized by fragile skin, woolly hair, and thickened skin on the palms and soles. | desmoplakin | ||||
| 376 | Sneddon syndrome | ADA2 | A condition characterized by livedo reticularis (a skin rash) and recurrent stroke-like episodes. | adenosine deaminase 2 | ||||
| 377 | Sorsby fundus dystrophy | TIMP3 | A retinal dystrophy causing progressive vision loss and degeneration of the retinal pigment epithelium. | TIMP metallopeptidase inhibitor 3 | ||||
| 378 | SPECC1L-related hypertelorism syndrome | SPECC1L | A genetic condition characterized by widely spaced eyes (hypertelorism) and other developmental abnormalities. | sperm antigen with calponin homology and coiled-coil domains 1 like | ||||
| 379 | Spinocerebellar ataxia type 17 | TBP | A neurodegenerative disorder leading to progressive loss of coordination and balance, associated with mutations in the SCFD1 gene. | TATA-box binding protein | ||||
| 380 | Spinocerebellar ataxia type 18 | IFRD1 | A genetic disorder causing progressive ataxia, with associated cognitive and movement issues. | interferon related developmental regulator 1 | ||||
| 381 | Spinocerebellar ataxia type 1 | ATXN1 | A hereditary ataxia disorder causing progressive degeneration of the cerebellum, leading to impaired coordination and balance. | ataxin 1 | ||||
| 381 | Spinocerebellar ataxia type 1 | ATXN1 | A hereditary ataxia disorder causing progressive degeneration of the cerebellum, leading to impaired coordination and balance. | ataxin 1 | ||||
| 382 | Spinocerebellar ataxia type 26 | EEF2 | A form of spinocerebellar ataxia associated with progressive motor dysfunction and ataxia. | eukaryotic translation elongation factor 2 | ||||
| 383 | Spinocerebellar ataxia type 27 | FGF14 | A genetic disorder characterized by progressive cerebellar ataxia, affecting movement and coordination. | fibroblast growth factor 14 | ||||
| 384 | Spinocerebellar ataxia type 28 | AFG3L2 | A rare ataxia disorder leading to progressive loss of motor control and coordination. | AFG3 like matrix AAA peptidase subunit 2 | ||||
| 385 | Spinocerebellar ataxia type 4 | PLEKHG4 | A neurodegenerative disorder leading to progressive ataxia and motor dysfunction, associated with mutations in the KCNC3 gene. | pleckstrin homology and RhoGEF domain containing G4 | ||||
| 386 | Spinocerebellar ataxia type 5 | SPTBN2 | A genetic condition causing degeneration of the cerebellum and spinal cord, resulting in coordination and balance problems. | spectrin beta, non-erythrocytic 2 | ||||
| 387 | Spinocerebellar ataxia type 6 | CACNA1A | A hereditary ataxia disorder characterized by progressive ataxia and motor dysfunction. | calcium voltage-gated channel subunit alpha1 A | ||||
| 388 | Spinocerebellar ataxia type 7 | ATXN7 | A condition leading to progressive cerebellar ataxia, often associated with retinal degeneration. | ataxin 7 | ||||
| 389 | Spondyloepiphyseal dysplasia tarda, x-linked | TRAPPC2 | A type of skeletal dysplasia causing short stature and skeletal abnormalities, inherited in an X-linked pattern. | trafficking protein particle complex subunit 2 | ||||
| 390 | Spondyloepiphyseal dysplasia tarda | TRAPPC2 | A genetic disorder leading to skeletal abnormalities, short stature, and joint issues. | trafficking protein particle complex subunit 2 | ||||
| 391 | Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome | PCYT1A | A rare syndrome combining skeletal dysplasia with cone-rod dystrophy, affecting vision and bone development. | phosphate cytidylyltransferase 1A, choline | ||||
| 392 | Stiff skin syndrome | FBN1 | A rare connective tissue disorder causing rigid, thickened skin, often with restricted joint mobility. | fibrillin 1 | ||||
| 393 | STING-associated vasculopathy with onset in infancy | STING1 | A condition involving early-onset inflammation and blood vessel abnormalities due to STING gene mutations | stimulator of interferon response cGAMP interactor 1 | ||||
| 394 | Sturge-Weber syndrome | GNAQ | A neurocutaneous disorder characterized by a facial birthmark and neurological issues, often including seizures and developmental delays. | G protein subunit alpha q | ||||
| 395 | Syringocystadenoma papilliferum | BRAF | A benign skin tumor characterized by cystic lesions and papillary growths, usually occurring on the scalp. | B-Raf proto-oncogene, serine/threonine kinase | ||||
| 396 | Systemic primary carnitine deficiency | SLC22A5 | A metabolic disorder caused by a deficiency in carnitine, leading to issues with fatty acid metabolism and energy production. | solute carrier family 22 member 5 | ||||
| 397 | Tangier disease | ABCA1 | A rare genetic disorder characterized by extremely low levels of high-density lipoprotein (HDL) cholesterol, leading to various health issues. | ATP binding cassette subfamily A member 1 | ||||
| 398 | Temple-Baraitser syndrome | NOG | A rare condition where there is an abnormal connection between the tarsal and carpal bones, affecting limb function. | noggin | ||||
| 399 | Telethonin-related limb-girdle muscular dystrophy R7 | TCAP | A type of limb-girdle muscular dystrophy linked to mutations in the telethonin gene, causing progressive muscle weakness. | titin-cap | ||||
| 400 | Temple-Baraitser syndrome | KCNH1 | A genetic disorder marked by developmental delay, intellectual disability, and distinctive facial features. | potassium voltage-gated channel subfamily H member 1 | ||||
| 401 | Temtamy preaxial brachydactyly syndrome | CHSY1 | A condition involving shortened fingers or toes (brachydactyly) and preaxial polydactyly (extra digits). | chondroitin sulfate synthase 1 | ||||
| 402 | Testicular seminomatous germ cell tumor | KIT | A cancer arising from testicular germ cells, often presenting as a painless testicular mass. | KIT proto-oncogene, receptor tyrosine kinase | ||||
| 403 | Tibial aplasia-ectrodactyly syndrome | BHLHA9 | A rare genetic disorder characterized by the absence of the tibia bone and abnormal digit development. | basic helix-loop-helix family member a9 | ||||
| 404 | Tibial hemimelia | GLI3 | A congenital condition where the tibia bone is either absent or severely underdeveloped, impacting leg function. | GLI family zinc finger 3 | ||||
| 404 | Treacher collins syndrome 3 | POLR1C | A genetic disorder leading to craniofacial abnormalities, including underdeveloped facial bones and ear malformations. | RNA polymerase I and III subunit C | ||||
| 405 | Trichomegaly-retina pigmentary degeneration-dwarfism syndrome | PNPLA6 | A rare condition involving excessive hair growth, retinal degeneration, and short stature. | patatin like phospholipase domain containing 6 | ||||
| 406 | TRIM32-related limb-girdle muscular dystrophy R8 | TRIM32 | A type of limb-girdle muscular dystrophy associated with mutations in the TRIM32 gene, resulting in progressive muscle weakness. | tripartite motif containing 32 | ||||
| 407 | Tufted angioma | GNA14 | A benign vascular tumor characterized by clusters of blood vessels, often appearing on the skin. | G protein subunit alpha 14 | ||||
| 408 | Tumor necrosis factor receptor 1 associated periodic syndrome | TNFRSF1A | A condition involving periodic fever episodes and skin rashes due to mutations affecting tumor necrosis factor receptor 1. | TNF receptor superfamily member 1A | ||||
| 409 | Tyrosinemia type 1 | FAH | A severe metabolic disorder caused by a deficiency in fumarylacetoacetate hydrolase, leading to liver and kidney damage. | fumarylacetoacetate hydrolase | ||||
| 410 | Ulnar-mammary syndrome | TAT | A metabolic disorder due to a deficiency in tyrosine aminotransferase, leading to neurological symptoms and eye problems. | tyrosine aminotransferase | ||||
| 411 | Ulnar-mammary syndrome | TBX3 | A genetic condition characterized by abnormalities of the ulnar bone and mammary glands, often associated with other developmental issues. | T-box transcription factor 3 | ||||
| 412 | Uveal coloboma-cleft lip and palate-intellectual disability | YAP1 | A condition involving eye abnormalities, cleft lip and/or palate, and intellectual disability. | Yes1 associated transcriptional regulator | ||||
| 413 | VACTERL with hydrocephalus | FANCB | A rare multiple congenital anomalies characterized by the association of Vertebral anomalies, Anal atresia, Congenital cardiac disease, Tracheoesophageal fistula, Renal anomalies, and Limb defects (acronym VACTERL) with hydrocephalus. Association with hydrocephalus is relatively rare, may be distinct from VACTERL association in general, and may follow an autosomal recessive pattern of inheritance in some individuals | FA complementation group B | ||||
| 414 | Van der woude syndrome 2 | GRHL3 | Van der Woude syndrome is a condition that affects the development of the face. Many people with this disorder are born with either a cleft lip or a cleft palate (an opening in the upper lip or roof of the mouth), or both. Affected individuals usually have depressions (pits) near the center of the lower lip, which may appear moist due to the presence of salivary and mucous glands in the pits. Small mounds of tissue on the lower lip may also occur. In some cases, people with van der Woude syndrome have missing teeth. | grainyhead like transcription factor 3 | ||||
| 415 | Vascular Ehlers-Danlos syndrome | COL3A1 | Vascular-type Ehlers-Danlos syndrome is a severe subtype of a genetic connective tissue disorder. People with this condition have very fragile tissues and are at high risk for severe bleeding and internal injuries. While it isn’t curable, this condition is often manageable, and the complications are often treatable. | collagen type III alpha 1 chain | ||||
| 416 | Vasculitis due to ADA2 deficiency | ADA2 | A vein of Galen malformation (VOGM) is a type of rare blood vessel abnormality inside the brain. In VOGM, misshapen arteries in the brain connect directly with veins, instead of connecting with capillaries, which help slow blood flow. This causes a rush of high-pressure blood into the veins. | adenosine deaminase 2 | ||||
| 417 | Vein of Galen aneurysmal malformation | EPHB4 | A vein of Galen malformation (VOGM) is a type of rare blood vessel abnormality inside the brain. In VOGM, misshapen arteries in the brain connect directly with veins, instead of connecting with capillaries, which help slow blood flow. This causes a rush of high-pressure blood into the veins. | EPH receptor B4 | ||||
| 418 | Warsaw breakage syndrome | DDX11 | A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by pre- and postnatal growth restriction, microcephaly, mild to severe intellectual disability, sensorineural hearing loss with cochlear abnormalities, and facial dysmorphism (with small and elongated face, bifrontal narrowing, epicanthus, short nose, small nares, dysplastic ears, and short neck). Additional variable features include limb malformations, cardiac anomalies, abnormal skin pigmentation, and recurrent infections, among others. | DEAD/H-box helicase 11 | ||||
| 419 | Werner syndrome | WRN | Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins to develop when they are in their twenties and includes graying and loss of hair; a hoarse voice; and thin, hardened skin. They may also have a facial appearance described as "bird-like." Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition. | WRN RecQ like helicase | ||||
| 420 | X-linked adrenal hypoplasia congenita | NR0B1 | X-linked adrenal hypoplasia congenita is a disorder that is noticeable from birth (congenital) and affects the development of the adrenal glands, which are hormone-producing (endocrine) organs (glands) located on top of each kidney. These glands produce a variety of hormones that regulate many essential functions in the body, such as response to stress. | nuclear receptor subfamily 0 group B member 1 | ||||
| 421 | X-linked cerebral adrenoleukodystrophy | ABCD1 | X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder that affects the white matter of the nervous system and the adrenal cortex. White matter is made up of nerve fibers called axons that relay nerve impulses from one cell to another. These nerve fibers are covered by myelin, an insulating layer or sheath that protects the nerve fibers. Myelin is made up of proteins and fats and gives white matter its white color. Without myelin, the signals between nerve cells cannot be transmitted properly, resulting in neurological symptoms. The adrenal cortex is the outer layer of cells of the adrenal glands. The adrenal glands sit atop the kidneys and produce hormones that are vital to proper health and development including cortisol and the sex hormones. Many of those affected experience serious neurological problems either during childhood or during adulthood with rather different types of disabilities. Some affected individuals also have adrenal insufficiency, which means that reduced amounts of certain hormones such as adrenaline and cortisol are produced, leading to abnormalities in blood pressure, heart rate, sexual development and reproduction. ALD is an X-linked recessive disorder that is caused by variations (mutations) in the ABCD1 gene. Because it is an X-linked disorder males develop more serious complications than females, while some females will have no symptoms. ALD can be broken down into different types based on symptoms and age of onset. | ATP binding cassette subfamily D member 1 | ||||
| 422 | X-linked dominant chondrodysplasia punctata | EBP | A rare genodermatosis disease with great phenotypic variation and characterized most commonly by ichthyosis following the lines of Blaschko, chondrodysplasia punctata (CDP), asymmetric shortening of the limbs, cataracts and short stature. | EBP cholestenol delta-isomerase | ||||
| 423 | X-linked dystonia-parkinsonism | TAF1 | X-linked dystonia-parkinsonism is a movement disorder that has been found only in people of Filipino descent. This condition affects men much more often than women. Parkinsonism is usually the first sign of X-linked dystonia-parkinsonism. Parkinsonism is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling gait that can cause recurrent falls | TATA-box binding protein associated factor 1 | ||||
| 424 | X-linked intellectual disability, Najm type | CASK | Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development | calcium/calmodulin dependent serine protein kinase | ||||
| 425 | X-linked intellectual disability, Siderius type | PHF8 | X-linked intellectual disability, Siderius type is characterised by mild to borderline intellectual deficit associated with cleft lip/palate. Preaxial polydactyly, large hands and cryptorchidism are sometimes present. The syndrome has been described in seven boys from two families. Transmission is X-linked and the syndrome is caused by mutations in the PHF8 gene, localised to the p11.21 region of the X chromosome. | PHD finger protein 8 | ||||
| 426 | X-linked myopathy with excessive autophagy | VMA21 | .X-linked myopathy with excessive autophagy (XMEA) is a very rare genetic condition. Autophagy is the process of breaking down damaged or unnecessary cell parts such as proteins and organelles. The most common feature of XMEA is muscle disease (myopathy) and slowly worsening muscle weakness, especially in the legs. This disorder is caused by a harmful change (mutation) in the VMA21 gene located on the X chromosome. The inheritance pattern of XMEA is X-linked, meaning that typically only males are affected and females are unaffected carriers. | vacuolar ATPase assembly factor VMA21 | ||||
| 427 | X-linked retinoschisis | RS1 | X-linked juvenile retinoschisis is a condition characterized by impaired vision that begins in childhood and occurs almost exclusively in males. This disorder affects the retina, which is a specialized light-sensitive tissue that lines the back of the eye. Damage to the retina impairs the sharpness of vision (visual acuity) in both eyes. Typically, X-linked juvenile retinoschisis affects cells in the central area of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. X-linked juvenile retinoschisis is one type of a broader disorder called macular degeneration, which disrupts the normal functioning of the macula. Occasionally, side (peripheral) vision is affected in people with X-linked juvenile retinoschisis | retinoschisin 1 | ||||
| 428 | X-linked severe congenital neutropenia | WAS | X-linked severe congenital neutropenia is an immunodeficiency syndrome characterized by recurrent major bacterial infections, severe congenital neutropenia, and monocytopenia. It has been described in five males spanning three generations of one family. It is transmitted as an X-linked recessive trait and is caused by mutations in the WAS gene, encoding the WASP protein. | WASP actin nucleation promoting factor | ||||
| 429 | X-linked sideroblastic anemia | ALAS2 | .X-linked sideroblastic anemia is a constitutional microcytic, hypochromic anemia of varying severity that is clinically characterized by manifestations of anemia and iron overload and that may respond to treatment with pyridoxine and folic acid. | 5'-aminolevulinate synthase 2 | ||||
| 430 | X-linked thrombocytopenia with normal platelets | WAS | X-linked thrombocytopenia is a bleeding disorder that primarily affects males. This condition is characterized by a blood cell abnormality called thrombocytopenia, which is a shortage in the number of blood cells involved in clotting (platelets). Affected individuals often have abnormally small platelets as well, a condition called microthrombocytopenia. X-linked thrombocytopenia can cause individuals to bruise easily or have episodes of prolonged bleeding following minor trauma or even in the absence of injury (spontaneous bleeding). Some people with this condition experience spontaneous bleeding in the brain (cerebral hemorrhage), which can cause brain damage that can be life-threatening. | WASP actin nucleation promoting factor | ||||
| 431 | Jervell and Lange-Nielsen Syndrome | 1 to 6 people per 1,000,000. | KCNQ1 , KCNE1 | LQT; RWS; WRS; LQT1; SQT2; ATFB1; ATFB3; JLNS1; KCNA8; KCNA9; Kv1.9; Kv7.1; KVLQT1 | Jervell and Lange Nielsen syndrome (JLNS) is a rare autosomal recessive disorder characterized by bilateral sensorineural hearing loss and a prolonged QTc interval (usually more than 500 msec), which can lead to Torsades de pointes and sudden cardiac death. It is a form of an inherited long QT syndrome (LQTS). The disease was first described in 1957 by Anton Jervell and Fred Lange-Nielsen in a study of 4 children born with congenital deafness that all suffered from syncope. There was a marked prolongation of the QT interval on electrocardiographic studies with no other identifiable cause for the patient’s fainting spells. | KCNQ1-potassium voltage-gated channel subfamily Q member 1 KCNE1-potassium voltage-gated channel subfamily E regulatory subunit 1 | ||
| 432 | Angelman syndrome (AS) | Angelman syndrome (AS) affects an estimated 1 in 12,000 to 20,000 people worldwide | UBE3A(ubiquitin-protein ligase E3A) | ANCR, AS, E6-AP, EPVE6AP, HPVE6A, PIX1 | Angelman syndrome (AS) is a rare neurogenetic disorder that causes a range of physical and behavioral characteristics. Every individual living with AS is unique. However, many signs and symptoms of Angelman syndrome are common across most individuals diagnosed with the condition. AS is a spectrum disorder, which means that not all individuals have the exact same characteristics or degree of severity.Angelman syndrome is a rare neurogenetic disorder caused by the loss of function of the UBE3A gene (ubiquitin-protein ligase E3A) located on chromosome 15q11-q13. Maternal imprinting: Normally, only the maternal UBE3A gene is active in neurons; the paternal copy is silenced. If the maternal copy is missing or nonfunctional → no UBE3A activity in the brain → Angelman syndrome. | |||
| 433 | Joubert syndrome | TCTN1 | JBTS13, TECT1 | Joubert syndrome is a rare genetic condition characterized by abnormal brain development that includes the absence or underdevelopment of the cerebellar vermis (an area of the brain that controls balance and coordination) and a malformed brain stem. It can be inherited (both parents must have a copy of one of the many gene mutations that causes the disorder) or sporadic (happening on its own). | ||||
| 434 | Hereditary hemorrhagic telangiectasia (HHT) | The current prevalence estimates for HHT are approximately 1 in 5000 worldwide. | ENG(endoglin) | END, HHT1, ORW1 | Hereditary hemorrhagic telangiectasia (HHT), also called Rendu–Osler syndrome, is a rare genetic disease characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes. The current prevalence estimates for HHT are approximately 1 in 5000 worldwide. ENG upregulation in microglia enhances pro-inflammatory signaling (via TGF-β/Smad pathways).Vascular dysfunction: High ENG → impaired endothelial function, abnormal angiogenesis, BBB leakage.Amyloid pathology (in AD): Altered ENG expression affects clearance of amyloid-β across the BBB.Neurovascular unit (NVU) breakdown: In ALS/AD/PD, ENG contributes to loss of NVU integrity, linking vascular pathology to neuronal death. | |||
| 435 | Congenital adrenal hyperplasia (CAH) | The classic forms of 21-hydroxylase deficiency affect roughly 1 in 15,000 to 1 in 20,000 live births in Western populations, while the nonclassic form is more common, around 1 in 1,000 in the general population, and much more frequent in some ethnic groups like the Ashkenazi Jewish population. | CYP21A2( cytochrome P450 family 21 subfamily A member 2) | CA21H, CAH1, CPS1, CYP21, CYP21B, P450c21B | Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders caused by complete or partial defects in one of the several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 95–99% of all cases of CAH are caused by deficiency of steroid 21-hydroxylase, an enzyme encoded by the CYP21A2 gene. Currently, CYP21A2 genotyping is considered a valuable complement to biochemical investigations in the diagnosis of 21-hydroxylase deficiency. | |||
| 436 | Congenital hyperekplexia | Its prevalence varying but consistently described as rare, ranging from less than 1 in 1,000,000 to approximately 1 in 40,000 people in the United States | SLC6A5 (solute carrier family 6 member 5) | GLYT-2, GLYT2, HKPX3, NET1 | Argininosuccinate lyase deficiency (ASLD), also known as argininosuccinic aciduria, is an autosomal-recessive urea cycle disorder caused by loss-of-function variants in ASL ASLD, like other urea cycle defects, impairs the disposal of nitrogen and leads to hyperammonemia. It can present as a neonatal life-threatening condition with lethargy, vomiting, seizures, and coma. These symptoms can also arise later in life during a catabolic state. The long-term sequelae include epilepsy, developmental impairment, and liver disease. The incidence of ASLD in the US and Europe has been estimated in the most recent reports to be from 1:190,000 to 1:219,000 live births,4,5 and in Finland 1:144,000.6 | |||
| 437 | 3p deletion syndrome | 3p deletion syndrome is a rare condition, with an estimated prevalence of less than 1 in 1,000,000 people worldwide | CNTN4 (contactin 4) | AXCAM, BIG-2 | 3p deletion syndrome is a rare contiguous-gene disorder involving the loss of the telomeric portion of the short arm of chromosome 3 and characterized by developmental delay, growth retardation, and dysmorphic features.CNTN4 is sufficient to confer key aspects of the 3p deletion syndrome phenotype, including developmental delay. Thus, CNTN4 is one of a relatively small number of autosomal genes identified as contributing to cognitive deficits in a contiguous-gene syndrome. It is interesting to note that many features of a presumed multigene phenotype are manifested as the result of the disruption of only a single transcript. This finding provides a rationale for mutation screening of CNTN4 in selected patients with developmental delay and dysmorphic features who have normal karyotypes | |||
| 438 | Argininosuccinate lyase deficiency (ASLD) or argininosuccinic aciduria | The incidence of ASLD in the US and Europe has been estimated in the most recent reports to be from 1:190,000 to 1:219,000 live births,4,5 and in Finland 1:144,000.6 | ASL variant 2 | ASALD, ASL | Argininosuccinate lyase deficiency (ASLD), also known as argininosuccinic aciduria, is an autosomal-recessive urea cycle disorder caused by loss-of-function variants in ASL ASLD, like other urea cycle defects, impairs the disposal of nitrogen and leads to hyperammonemia. It can present as a neonatal life-threatening condition with lethargy, vomiting, seizures, and coma. These symptoms can also arise later in life during a catabolic state. The long-term sequelae include epilepsy, developmental impairment, and liver disease. The incidence of ASLD in the US and Europe has been estimated in the most recent reports to be from 1:190,000 to 1:219,000 live births,4,5 and in Finland 1:144,000.6 | |||
| 439 | Hereditary Coproporphyria (HCP) | The incidence of active HCP appears to be at most 2 cases per 1,000,000 people. | CPOX (coproporphyrinogen oxidase) | COX, CPO, CPX, HARPO, HCP | The rare disease caused by mutations in the CPOX gene is Hereditary Coproporphyria (HCP), a type of acute hepatic porphyria, characterized by neurovisceral attacks, psychiatric symptoms, seizures, and sometimes photosensitive skin lesions. | |||
| 440 | Classic Ehlers–Danlos syndrome | The prevalence of classic Ehlers–Danlos syndrome (cEDS) is estimated to be between 1 in 20,000 and 1 in 40,000 individuals. | COL5A1 (collagen type V alpha 1 chain) | EDSC, EDSCL1, FMDMF | Classic Ehlers–Danlos syndrome is a heritable disorder of connective tissue that is characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. Mutations in the COL5A1 and the COL5A2 gene, encoding the α1 and the α2-chain of type V collagen respectively, are identified in approximately 50% of patients with a clinical diagnosis of classic EDS. | |||
| 441 | Chediak-Higashi syndrome (CHS) | Chediak-Higashi syndrome (CHS) is a rare disorder with an estimated incidence of less than 1 in 1,000,000 births | (LYST) lysosomal trafficking regulator | CHS, CHS1, Mauve | Chediak-Higashi syndrome (CHS), over 75 years ago, several studies have been conducted to underscore the role of the lysosomal trafficking regulator (LYST) gene in the pathogenesis of disease. CHS is a rare autosomal recessive disorder, which is caused by biallelic mutations in the highly conserved LYST gene. The disease is characterized by partial oculocutaneous albinism, prolonged bleeding, immune and neurologic dysfunction, and risk for the development of hemophagocytic lympohistiocytosis (HLH) | |||
| 442 | Aplasia cutis congenita (ACC) | CC is a rare congenital condition with an incidence of approximately 1 to 3 out of 10,000 births. | KCTD1 (potassium channel tetramerization domain containing 1) | C18orf5 | Aplasia cutis congenita (ACC) is a congenital epidermal defect of the midline scalp and has been proposed to be due to a primary keratinocyte abnormality. Why it forms mainly at this anatomic site has remained a long-standing enigma. KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities. Here, we found that KCTD1 and KCTD15 can form multimeric complexes and can compensate for each other’s loss and that disease mutations are dominant negative, resulting in lack of KCTD1/KCTD15 function. We demonstrated that KCTD15 is critical for cardiac outflow tract development, whereas KCTD1 regulates distal nephron function. Combined inactivation of KCTD1/KCTD15 in keratinocytes resulted in abnormal skin appendages but not in ACC. Instead, KCTD1/KCTD15 inactivation in neural crest cells resulted in ACC linked to midline skull defects, demonstrating that ACC is not caused by a primary defect in keratinocytes but is a secondary consequence of impaired cranial neural crest cells, giving rise to midline cranial suture cells that express keratinocyte-promoting growth factors.ACC is a rare congenital condition with an incidence of approximately 1 to 3 out of 10,000 births. | |||
| 443 | FTLD-FUS: Frontotemporal lobar degeneration with FUS pathology | While the overall incidence of FTLD is about 10.8 per 100,000, specific figures for FTLD-FUS are not as readily available due to its rarity. | SYNCRIP synaptotagmin binding cytoplasmic RNA interacting protein | GRY-RBP, GRYRBP, HNRNPQ, HNRPQ1, NSAP1, PP68, hnRNP-Q | Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of pathologies that present clinically with progressive changes in behavior, personality, and executive function with variable amounts of motor impairment, FTLD-FUS (Frontotemporal Lobar Degeneration with FUS pathology) is a rare subtype of FTLD, representing approximately 5-10% of all FTLD cases.characterized by cytoplasmic inclusions of fused in sarcoma (FUS) protein, and is often associated with a severe behavioral variant of frontotemporal dementia, While the overall incidence of FTLD is about 10.8 per 100,000, specific figures for FTLD-FUS are not as readily available due to its rarity. | |||
| 444 | Meckel-Gruber syndrome (MKS) | The worldwide prevalence of Meckel–Gruber syndrome (MKS) is estimated to be 1 in 13,250 to 140,000 live births, though this can vary significantly by population due to genetic factors. For example, MKS is much more common in populations with high rates of consanguineous marriages, such as in India and some Arab countries | TCTN1 | JBTS13, TECT1 | Meckel–Gruber syndrome (MKS) is a lethal autosomal recessive congenital anomaly syndrome caused by mutations in genes encoding proteins that are structural or functional components of the primary cilium. Conditions that are caused by mutations in ciliary genes are collectively termed the ciliopathies, and MKS represents the most severe condition in this group of disorders.Meckel–Gruber syndrome is a lethal developmental syndrome characterized by posterior fossa abnormalities (most frequently occipital encephalocele) , bilateral enlarged cystic kidneys and hepatic developmental defects that include ductal plate malformation associated with hepatic fibrosis and cysts . A common additional feature is postaxial polydactyly, usually affecting both hands and feet Other occasional features, seen in 25–40% of fetuses include bowing and shortening of the long bones, abnormalities of the male genitalia, microcephaly or anencephaly, cleft lip and palate, and other craniofacial abnormalities, congenital heart defects, and pulmonary hypoplasia .Rare features (seen in less than 20% of cases) include cystic dysplasia of the lungs or thyroid, retinal colobomata, and situs defects Central nervous system (CNS) defects are considered to be obligate features of MKS but appear to have a variable presentation, varying between total craniorachischisis, partial defects of the corpus callosum, Dandy–Walker malformation, and most frequently occipital encephalocele | |||
| 445 | KBG SYNDROME | The precise prevalence of KBG syndrome is unknown and considered rare, with some sources stating fewer than 1 in 1,000,000 births, while others emphasize it is likely underdiagnosed. | ANKRD1 (ankyrin repeat domain containing 11) | ANCO-1, ANCO1, LZ16, T13 | KBG syndrome is characterized by macrodontia of upper central incisors, distinctive craniofacial features such as triangular face, prominent nasal bridge, thin upper lip and synophrys; skeletal findings including short stature, delayed bone age, and costovertebral anomalies; and developmental delay/intellectual disability sometimes associated with seizures and EEG abnormalities. The condition was named KBG syndrome after the initials of the last names of three original families reported in 1975. | |||
| 446 | Congenital muscular dystrophy (CMD) | The prevalence of Congenital Muscular Dystrophy (CMD) is estimated to be around 0.6 to 0.9 per 100,000 people or roughly 1 in 100,000 to 160,000, though prevalence figures vary by study and location. | ITGA7 | Integrin Subunit Alpha 7 Integrin Alpha-7 Integrin Alpha 7 Chain 3 Integrin, Alpha 7 | Congenital muscular dystrophy (CMD) is a group of hereditary muscular dystrophy beginning at birth or early life. The clinical manifestations are postnatal hypotonia and motor development, joint contracture, and increased serum creatine kinase (CK). A rare case of a boy from a consanguineous family diagnosed with CMD caused by ITGA7 mutation. | |||
| 447 | MARSHALL SYNDROME | Marshall syndrome is an extremely rare genetic disorder usually diagnosed in infancy with a prevalence of < 1 in 1 million | COL11A1 | CO11A1, COLL6, DFNA37, STL2 | Marshall syndrome is a rare, autosomal dominant skeletal dysplasia that is phenotypically similar to the more common disorder Stickler syndrome. For a large kindred with Marshall syndrome, we demonstrate a splice-donor-site mutation in the COL11A1 gene that cosegregates with the phenotype. The G+1-->A transition causes in-frame skipping of a 54-bp exon and deletes amino acids 726-743 from the major triple-helical domain of the alpha1(XI) collagen polypeptide. The data support the hypothesis that the alpha1(XI) collagen polypeptide has an important role in skeletal morphogenesis that extends beyond its contribution to structural integrity of the cartilage extracellular matrix. Our results also demonstrate allelism of Marshall syndrome with the subset of Stickler syndrome families associated with COL11A1 mutations. Marshall syndrome is an extremely rare genetic disorder usually diagnosed in infancy with a prevalence of < 1 in 1 million | |||
| 448 | Congenital myopathies | The overall prevalence of congenital myopathy in the general population is estimated to be around 1 to 5 per 100,000 live births, or about 1.5 per 100,000 in the all-age population, and 2.73 per 100,000 in the pediatric population. Specific congenital myopathies, such as nemaline myopathy or core myopathy, have lower estimated prevalences, with nemaline myopathy being around 0.20 per 100,000 in the all-age population. | RYR1 | CCO, CMYO1A, CMYO1B, CMYP1A, CMYP1B, KDS, MHS, MHS1, PPP1R137, RYDR, RYR, RYR-1, SKRR | Congenital myopathies are a rare group of inherited muscle disorders present at birth, characterized by muscle weakness (hypotonia) and a generally static or slowly progressive course, rather than worsening over time. They are identified by specific structural features on a muscle biopsy, such as nemaline myopathy (rods), central core disease (cores), or centronuclear myopathy (central nuclei). While there is no cure, treatment involves supportive measures like physical, occupational, and speech therapy to manage symptoms and preserve function. Congenital means “present at birth” and myopathy means “disease of muscle.” Babies with congenital myopathies lack muscle tone at birth. Other signs of the condition include skeletal problems (like weak or improperly aligned bones), difficulty breathing and feeding issues. Symptoms can appear at birth, during infancy or throughout childhood. | |||
| 449 | Disseminated gonococcal infection | Disseminated gonococcal infection (DGI) is rare, affecting an estimated 0.5% to 3% of people with gonorrhea | complement C7 | Complement Component C7 Complement Component 7 | Disseminated gonococcal infection (DGI) is a rare but serious complication of untreated gonorrhea, caused by the bacteria Neisseria gonorrhoeae spreading into the bloodstream. DGI can lead to arthritis, skin lesions, and tenosynovitis (inflammation of tendon sheaths), often presenting as the "arthritis-dermatitis syndrome". Diagnosis involves testing blood, synovial fluid, or skin lesions, and treatment typically requires intravenous antibiotics, such as ceftriaxone and azithromycin.Disseminated gonococcal infection (DGI) symptoms include a triad of arthritis-dermatitis syndrome (joint pain, skin rash, and inflammation of tendon sheaths [tenosynovitis]), and septic arthritis (swollen, painful joints). Patients may also experience systemic symptoms like fever and chills. The rash typically appears as pustular or hemorrhagic lesions on the hands and feet. | |||
| 450 | Fibrochondrogenesis | Fibrochondrogenesis is an extremely rare genetic disorder with a reported worldwide prevalence of less than 1 in 1,000,000 births, though specific regional studies, particularly those including populations with high rates of consanguineous marriages, show higher incidences, such as one study in the United Arab Emirates (UAE) finding a prevalence of 1.05 per 10,000 births. | COL11A1 | CO11A1, COLL6, DFNA37, STL2 | A rare, rhizo-mesomelic dysplasia characterized by distinct facial features (flat midface, flat small nose, anteverted nares, low set ears, protuberant eyes, and small mouth with long upper lip), markedly short limbs with relatively normal hands and feet, short ribs with broad metaphyses and small bell-shaped thorax with protuberant abdomen. Vertebral bodies are flat, creating a distinctive pinched appearance in lateral radiographic views. Cleft palate, micrognathia, bifid tongue and brachyclinodactyly with some soft tissue syndactyly have been reported in few patients. It is mostly a neonatally lethal condition. Affected individuals who survive the neonatal period persents with severe global developmental delay, severe skeletal dysplasia, high myopia and mild to moderate hearing loss. | |||
| 451 | Hypophosphatemic Nephrolithiasis/Osteoporosis Type 1 (NPHLOP1) | While NF1 has a worldwide incidence of about 1 in 2,500–3,000 individuals, this bone and kidney complication is considered an uncommon manifestation of the disorder, occurring primarily in adulthood and often developing in later life. | SLC34A1. | FRTS2, HCINF2, NAPI-3, NPHLOP1, NPT2, NPTIIa, SLC11, SLC17A2 | A novel germline heterozygous mutation was identified in the SLC34A1 gene, c.1627G>T (p.Gly543Cys), currently not reported in databases of human gene mutations and scientific literature. SLC34A1 germline heterozygous mutations have been associated with the autosomal dominant hypophosphatemic nephrolithiasis/osteoporosis type 1 (NPHLOP1). It is characterized by renal phosphate wasting, leading to hypophosphatemia and the development of kidney stones and/or reduced bone mineral density (osteoporosis) in adults. Mechanism: A single mutated allele is enough to cause reduced NaPi-IIa function. This leads to persistent phosphate leakage into the urine, resulting in the associated bone and kidney problems over time. | |||
| 452 | Fanconi renotubular syndrome (FRTS) | Fanconi renotubular syndrome (FRTS) is a rare inherited disorder, but specific prevalence data is limited due to its varied causes, including conditions like nephropathic cystinosis, which is the most common inherited form with a global incidence of 1 in 100,000 to 200,000 live births | SLC34A1. | FRTS2, HCINF2, NAPI-3, NPHLOP1, NPT2, NPTIIa, SLC11, SLC17A2 | Many disorders of the proximal tubule, collectively referred to as proximal tubulopathies or Fanconi renotubular syndrome (FRTS), are associated with severe morbidities. Indeed, dysfunction of this nephron segment results in extreme metabolic disturbances owing to an inability to reabsorb critical molecules filtered by the kidneys, such as bicarbonate, calcium, or phosphate. | |||
| 453 | Atrial standstill | GJA5 | Connexin-40 gene (Cx40) and the gap junction protein alpha-5 gene | Atrial Standstill (AS) is a rare cardiac disorder characterized by the complete absence of electrical and mechanical activity in the atria, often resulting in absent P waves on an electrocardiogram (ECG) and bradycardia | ||||
| 454 | Progessive cardiac conduction diseases | The exact prevalence of progressive cardiac conduction disease (PCCD) is not clearly defined as a single global figure but is estimated to be about 1:2000 for genetically based forms, while in developed countries, it accounts for approximately 0.15 pacemaker implantations per 1,000 inhabitants per year and is one of the most common worldwide causes of pacemaker insertion | GJA5 | Connexin-40 gene (Cx40) and the gap junction protein alpha-5 gene | Progressive Cardiac Conduction Disease (PCCD) is a rare disorder, often genetic and familial, that causes progressive slowing of the heart's electrical signals, leading to heart block. It can manifest as a primary electrical disorder or be associated with other structural heart conditions. While there are age-related, non-genetic forms, the inheritance of a specific genetic mutation makes the condition rare and can lead to serious complications like syncope and sudden death | |||
| 455 | Limb-Girdle Muscular Dystrophy Type 2E (LGMD2E) | Mutations in the SGCB gene are a known cause of limb-girdle muscular dystrophy type 2E (LGMD2E). The exact prevalence of SGCB-associated LGMD is not clearly defined globally, but limb-girdle muscular dystrophies overall affect approximately 1 in 14,500 to 1 in 123,000 individuals, with SGCB mutations accounting for an estimated 5–10% of autosomal recessive LGMD cases. LGMD2E is more commonly reported in populations with higher rates of consanguinity, and patients typically present with progressive weakness of the shoulder and pelvic girdle muscles during childhood or adolescence. | SCGB | Beta-Sarcoglycan, LDB3-associated beta-sarcoglycan, B-SG, MGC14229 | The SGCB gene, or sarcoglycan beta, encodes the protein beta-sarcoglycan, a component of the sarcoglycan complex within the dystrophin-associated glycoprotein complex (DGC). Located on chromosome 4, it plays a critical role in maintaining muscle cell membrane integrity and stability during contraction. It is primarily expressed in skeletal and cardiac muscle, and mutations in this gene cause limb-girdle muscular dystrophy type 2E (LGMD2E). |