Genetic basis of pediatric epilepsy syndromes.

Abstract

Childhood epilepsy affects ~0.5–1% in the general population worldwide. Early-onset epileptic encephalopathies are considered to be severe neurological disorders, which lead to impaired motor, cognitive, and sensory development due to recurrence of seizures. Many of the observed epilepsy phenotypes are associated with specific chromosomal imbalances and thus display gene dosage effects, and also specific mutations of a variety of genes ranging from ion channels to transcription factors. High throughput sequencing technologies and whole exome sequencing have led to the recognition of several new candidate genes with a possible role in the pathogenesis of epileptic encephalopathies. The mutations causing channelopathies can be either a gain or a loss of ion channel function and contribute to the pathogenesis of epilepsy syndrome. Nearly 300 mutations of SCN1A gene coding for the Nav1.1 channel protein have been identified that contribute to the pathology of epilepsy. Besides Na, potassium and calcium channels are also implicated in epileptic encephalopathies. Therapeutic management of epileptic encephalopathies has been challenging as the majority of the medications are not efficient and often have many undesirable side effects. A better understanding of the molecular nature of epilepsy in an individual is important to design a personalized medication, considering the number of possible genetic mutations that can contribute to epileptic encephalopathies.