Epileptic Encephalopathy, Early Infantile, 1 (ARX)
| Dred_ID | RD00020 |
| OMIM ID | 308350 |
| Disease name | Epileptic Encephalopathy, Early Infantile, 1 |
| Alternative names | EIEE1 Infantile Spasm Syndrome, X-linked 1 Issx1 West Syndrome, X-linked Ohtahara Syndrome, X-linked Infantile Epileptic-dyskinetic Encephalopathy Xmesid |
| Category | Genetic diseases, Neuronal diseases, Rare diseases, Mental diseases, Liver diseases, Metabolic diseases, Muscle diseases, Eye diseases, Fetal diseases |
| Phenotype | OMIM: Early infantile epileptic encephalopathy is a severe form of epilepsy first reported by Ohtahara et al. (1976). It is characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Approximately 75% of EIEE patients progress to 'West syndrome,' which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG (Kato et al., 2007). Deprez et al. (2009) reviewed the genetics of epilepsy syndromes starting in the first year of life and included a diagnostic algorithm. EIEE1 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1) to syndromic (309510) and nonsyndromic (300419) mental retardation. Although males with ARX mutations are often more severely affected, female mutation carriers may also be affected (Kato et al., 2004; Wallerstein et al., 2008). |
| Miscellaneouse | OMIM: onset of seizures in first months of life (usually 4 to 7 months) dyskinesias occur in a subset of patients later than seizures (6 to 12 months) males are most severely affected, but females can also be affected |
| Prevalence | Prevalence: <1/1000000 (Worldwide) [source: MalaCards] |
| Inheritance | X-linked recessive |
| Anticipation | N/A |
| Evidence | Strong |
| Gene symbol | ARX |
| Alias symbols | ISSX; PRTS; CT121; EIEE1; MRX29; MRX32; MRX33; MRX36; MRX38; MRX43; MRX54; MRX76; MRX87; MRXS1 |
| Gene name | aristaless related homeobox |
| Gene map locus | Xp21.3; chrX:25,003,694-25,016,420(-) |
| Ensembl Gene ID | ENSG00000004848 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene is a homeobox-containing gene expressed during development. The expressed protein contains two conserved domains, a C-peptide (or aristaless domain) and the prd-like class homeobox domain. It is a member of the group-II aristaless-related protein family whose members are expressed primarily in the central and/or peripheral nervous system. This gene is thought to be involved in CNS development. Expansion of a polyalanine tract and other mutations in this gene cause X-linked mental retardation and epilepsy. [provided by RefSeq, Jul 2016] |
| Repeat unit | GCG |
| Normal repeat copies | 10-16 |
| Pathogenic repeat copies | ≥17 |
| Gene | ARX |
| Repeat location | CDS |
| Chromosome locus | chrX:25013653-25013691 (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | This gene is a homeobox-containing gene expressed during development. The expressed protein contains two conserved domains, a C-peptide (or aristaless domain) and the prd-like class homeobox domain. It is a member of the group-II aristaless-related protein family whose members are expressed primarily in the central and/or peripheral nervous system. This gene is thought to be involved in CNS development. Mutations in this gene cause X-linked mental retardation and epilepsy |
| Pathway annotation | Reactome, KEGG |
| PMID | 17664401 |
| Authors | Guerrini R, Moro F, Kato M, Barkovich AJ, Shiihara T, McShane MA, Hurst J, Loi M, Tohyama J, Norci V, Hayasaka K, Kang UJ, Das S, Dobyns WB |
| Title | Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus |
| Journal | Neurology. 69(5):427-33 |
| Year | 2007 |
| PMID | 17668384 |
| Authors | Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M, Tohyama J, Akasaka N, Hayasaka K |
| Title | A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome) |
| Journal | Am J Hum Genet. 81(2):361-6 |
| Year | 2007 |
| PMID | 23246292 |
| Authors | Poeta L, Fusco F, Drongitis D, Shoubridge C, Manganelli G, Filosa S, Paciolla M, Courtney M, Collombat P, Lioi MB, Gecz J, Ursini MV, Miano MG |
| Title | A regulatory path associated with X-linked intellectual disability and epilepsy links KDM5C to the polyalanine expansions in ARX |
| Journal | Am J Hum Genet. 92(1):114-25 |
| Year | 2013 |