Single Gene Mutations Causing Epileptogenic Malformations of the Cerebral Cortex

Several epilepsy syndromes associated with abnormal cortical development have been recognized for which causative gene defects have been identified. Lissencephaly (LIS) and subcortical band heterotopia (SBH) result from mutations of either the LIS1 or the DCX gene. Periventricular nodular heterotopia (PNH) features subset of neurons that have failed to migrate and therefore line the walls of the lateral ventricles. Mutations of the X-linked gene FLNA have been found in about 50% of all patients with bilateral PNH and in 100% of X-linked familial cases. A rare, recessive form of bilateral PNH is caused by mutations of the ARFGEF2 gene. There are several syndromes featuring polymicrogyria; among these syndromes, recessive bilateral frontoparietal polymicrogyria (BFPP) has been associated with mutations of the GPR56 gene and bilateral perisyilvian polymicrogyria (BPP) has been associated with SRPX2 mutations in isolated cases.