Genetics of Epilepsy: What for and How to Examine Children with Epilepsy E.D. Belousova

Abstract

The paper focuses on problems of genetic examination of children with epilepsy. The major types of monogenic epilepsies in children are described; clinical and research justification of molecular-genetic examination in these patients is given. Priority in molecular diagnosis should be given to epileptic syndromes with clear phenotype. In individuals with Dravet syndrome, detection of a typical mutation allows one to clarify the diagnosis and provides important data concerning prognosis and treatment strategy. If the phenotype is less clear, diagnostic panels need to be used to determine the most frequent mutations that cause severe epilepsy (epileptic encephalopathies). Thus, genetic studies provide new insights into epileptic encephalopathies with prolonged spike-wave activity during sleep: the GRIN2A gene encoding the alpha subunit of NMDA receptors was muted in 17.6% of children with this syndrome. The need for supplementing the examination algorithm of a child with severe epilepsy with comparative genomic hybridization is emphasized. In practical terms, detection of an epilepsy-causing muta- tion allows one to refuse further expensive diagnostic procedures, to predict the disease course more accurately (in some cases), to optimize the therapeutic strategy, and to determine the prognosis of further reproductive potential in some cases. Scientifically, studies into the sequelae of the known mutations (and their effect on child's brain development) allow one to refine the key processes of epileptogenesis. These data may be used to design new therapy methods (the so-called target therapy for epilepsy) in future.