Figure 1. Genetic etiology of epilepsy.

(A) 19 studies were reviewed in which patients with epilepsy were screened for genetic etiology, with cohort sizes ranging from 70 to 8565 individuals. See Table S1 for study details. Pathogenic variants were identified in 40% of patients. 45% of patients with pathogenic variants were identified in genes encoding ion channels and their accessory proteins (ligand gated ion channels were not included in this tally). Individuals with pathogenic variants in SCN1A were the most common followed by KCNQ2 and SCN2A. (B) Treemap of confirmed pathogenic ion channel variants associated with epilepsy separated by the type of channel (Na⁺, K⁺, Ca²⁺, Cl⁻, nonselective Na⁺/K⁺, or ion channel accessory protein genes). A list of all ion channel/accessory protein genes was used to perform a batch search for pathogenic variants identified in those genes using HGMD database. Variants were then manually cross referenced for clinical phenotypes related to epilepsy or seizures (including SUDEP that was not cardiac associated). (C) Numbers of variants reported to ClinVar database within each gene SCN1A, KCNQ2 and SCN2A separated by their pathogenicity profile.