Role of Genetics in the Etiopathogenesis of Genetic Generalized Epilepsy: A Review of Current Literature

ABSTRACT

"Until recently; genetic generalized epilepsy (GGE) was believed to be of presumed genetic etiology with no identifiable genetic mutation or demonstrable epigenetic abnormality. A wide range of epileptic disorders has clue for an inherited susceptibility. Monogenic disorders associated with epilepsy mental retardation and structural brain lesion typified by heterotopias; tuberous sclerosis; and progressive myoclonus epilepsies account for about 1 of epilepsies. This review focuses on the role of genetic mutations and epigenetic rearrangements in the pathophysiologic mechanism of GGE. To achieve this; PubMed; EMBASE; and Google Scholar were systematically and comprehensively searched using keywords (""epilepsy"" ""juvenile myoclonic epilepsy (JME);"" ""typical absences;"" ""idiopathic generalized epilepsy;"" ""JME;"" ""juvenile absence epilepsy;"" ""childhood absence epilepsy"" ""generalized tonic-clonic seizure"" ""GTCS""). Most GGE has evidence of underlying genetic inheritance. Recent animal studies have shown that early detection and treatment of genetic generalized epilepsies can alter the phenotypic presentation in rodents. These findings suggest a critical period in epileptogenesis; during which spike-and-wave seizures can be suppressed; leading to chronic changes in the brain (epileptogenesis) and the preceding dysfunctions may; therefore; be targeted using therapeutic approaches that may either delay or inhibit the transition to active epileptic attack. The interplay between genetic mutations and epigenetic rearrangements play important roles in the development of GCE and that this process; especially at crucial developmental periods; is very susceptible to environmental modulations"