Biallelic CNTN2 variants were first reported in individuals with epilepsy, tremors, and myoclonus in 2013 (Stogmann et al., PMID: 23518707). Since then, additional patients with homozygous CNTN2 variants have been reported with developmental delays/intellectual disability, most of whom also have epilepsy (PMIDs: 37359369, 34691156). Five variants (nonsense, frameshift) that have been reported in five probands in five publications are included in this curation (PMIDs: 23518707, 34691156, 36553572, 37359369, 28397838). Multiple affected individuals have been observed within families (PMIDs: 23518707, 37359369). This gene-disease relationship is also supported by a mouse model in which homozygous null CNTN2 mice present with spontaneous seizures (PMID: 11178983).
In summary, there is definitive evidence supporting the relationship between CNTN2 and autosomal recessive complex neurodevelopmental disorder. 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 GCEP on the meeting date November 7, 2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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