In contrast to non-syndromic MEG, HMEG is exclusively due to somatic mutations in PIK3CA, MTOR and AKT3 (172, 182, 241, 243) that result in a clinically severe phenotype, characterized by intractable epilepsy, severe ID, ipsilateral white matter anomalies, dilated/dysmorphic lateral ventricle, and cortical dysplasia. The gene discussed is PIK3CA; the disease is cerebral cortical dysplasia.