EMX2 was first reported in relation to autosomal dominant (AD) schizencephaly in 1996, reporting 3 patients with schizencephaly (Brunelli et al., PMID: 8528262). The same group reported 2 additional patients with schizencephaly in 1997, harboring a heterozygous germline variant in EMX2 (PMID: 9359037) and suggested that this was a common cause of schizencephaly. However, subsequent reports and case series screening for variants in EMX2 in cohorts of individuals with schizencephaly did not reveal any additional cases, calling into question the true rate of contribution of this gene to disease (PMID: 17506092, 18409201, 20157829). Overall, 4 variants (a missense, a frameshift, and two 3’ splice site mutations) have been reported in 4 probands across 2 publications (PMID: 8528262, 9359037). In summary, there is limited evidence to support this gene-disease relationship with individuals having a complex neurodevelopmental phenotype and seizures/epilepsy. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Epilepsy GCEP on September 3, 2024 (SOP v.11).
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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