ARX was reported in relation to Early Infantile Epileptic Encephalopathy in 2002 (Stromme et al. 2002). It is also reported in relation to intellectual disability (syndromic and nonsyndromic), hydranencephaly with abnormal genitalia, X-linked Lissencephaly, Partington syndrome, and Proud syndrome. Evidence included in this curation excluded individuals with syndromic diagnoses and/or intellectual disability. At least 18 unique variants (missense, in-frame indel, nonsense, frameshift and polyalanine repeat, etc.) have been reported in humans. Evidence supporting this gene-disease pair includes case-level data and experimental data. In summary, ARX is definitively associated with X-linked Early Infantile Epileptic Encephalopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on 6/4/19 (SOP version 6).
ARX was reported in relation to Early Infantile Epileptic Encephalopathy in 2002 (Stromme et al. 2002). It is also reported in relation to intellectual disability (syndromic and nonsyndromic), hydranencephaly with abnormal genitalia, X-linked Lissencephaly, Partington syndrome, and Proud syndrome. Evidence included in this curation focuses on individuals with seizure onset prior to 6 months of age and excludes individuals with syndromic diagnoses and/or intellectual disability. At least 18 unique variants (missense, in-frame indel, nonsense, frameshift and polyalanine repeat, etc.) have been reported in humans. Evidence supporting this gene-disease pair includes case-level data and experimental data. In summary, ARX is definitively associated with X-linked Early Infantile Epileptic Encephalopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on 6/4/19 (SOP version 6). As of 7/9/25, this record underwent administrative updates to provide additional information regarding the lumping and splitting of this gene. No new evidence has been reviewed or added.
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