Epilepsy genes: The link between molecular dysfunction and pathophysiology

Our understanding of the genetic basis of epilepsy is progressing at a rapi d pace. Gene mutations causing several of the inherited epilepsies have bee n mapped, and several more are likely to be added in coming years. In this review, we summarize the available information on the genetic basis of huma n epilepsies and epilepsy syndromes, emphasizing how genetic defects may co rrelate with the pathophysiological mechanisms of brain hyperexcitability. Mutations leading to epilepsy have been identified in genes encoding voltag e- and ligand-gated ion channels (benign familial neonatal convulsions, aut osomal dominant nocturnal frontal robe epilepsy, generalized epilepsy with febrile seizures "plus"), neurotransmitter receptors (Angelman syndrome), t he molecular cascade of cellular energy production (myoclonic epilepsy with ragged red fibers), and proteins without a known role in neuronal excitabi lity (Unverricht-Lundborg disease). Gene defects can lead to epilepsy by al tering multiple and diverse aspects of neuronal function. (C) 2000 Wiley-Li ss, Inc.