As the first variants reported for IQSEC2, high-throughput sequencing in ID and epilepsy cohorts has increasingly identified de novo loss-of-function IQSEC2 mutations in males and increasingly in females.19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 Complete abolition of enzymatic activity does not lead to lethality, but instead leads to a severe phenotype including epileptic encephalopathy in both males and females. The gene discussed is IQSEC2; the disease is epilepsy.