The Genetic Epilepsies

Human epilepsy (hEP) genes are those that have been demonstrated to directly cause epilepsy, and genetic epilepsy syndromes are defined as those that are associated with a hEP gene and/or show clear familial inheritance and do not result from gross structural brain abnormalities or metabolic derangements. Genetic epilepsy syndromes often arise at specific times in development. Here, we present the clinical features of nine developmentally specific genetic epilepsy syndromes, including benign familial neonatal epilepsy, infantile and childhood epileptic encephalopathies, febrile seizures, genetic epilepsy with febrile seizures plus (GEFS +), Dravet syndrome, childhood absence epilepsy, juvenile myoclonic epilepsy, autosomal dominant nocturnal frontal lobe epilepsy, and autosomal dominant epilepsy with auditory features. For each of these syndromes, we report their pattern of heritability and their association with hEP genes. The connection between genetic epilepsy syndromes and hEP genes is heterogeneous. Many genetic epilepsy syndromes are associated with diverse hEP genes, and some hEP genes associate with multiple genetic epilepsy syndromes. Finally, we discuss investigations into the pathophysiology of selected hEP mutations both when recombinant hEP genes were expressed in heterologous cells, and, when applicable, when the hEP mutations were introduced into knock-in mice.