Genetic Identifiers of Epilepsy

Abstract

Summary: Epilepsy affects >0.5% of the world's population and has a large genetic component. The most common human genetic epilepsies display a complex pattern of inheritance, and the identity of the susceptibility genes is largely unknown despite recent advances in molecular biology. However, genetic identifiers of certain types of epilepsy with neurodegenerative characteristics and of a small number of familial idiopathic epilepsies have been uncovered to date. This article reviews recent progress made in molecular genetics of epilepsy, focusing mostly on idiopathic epilepsy together with our own discovery of novel mutations in the genes of autosomal dominant nocturnal frontal lobe epilepsy and benign familial neonatal convulsions (BFNCs), and the genetic locus of benign adult familial myoclonic epilepsy. Pathogenesis of epilepsy as a channelopathy and of BFNC also is discussed. Key Words: Epilepsy genes-Autosomal dominant nocturnal frontal lobe epilepsy-Benign familial neonatal convulsions-Benign adult familial myoclonic epilepsy-Channelopathy.Epilepsy affects >0.5% of the world's population and has a large genetic component (1). The focus of research on the genetics of the epilepsies is the identification of mutations causing epilepsies, and the abnormal properties of the neuron glia system through the expressed mutations and result in clinical epilepsy. Once the mutated code scripts are identified in the epilepsies, it will lead to an understanding of how neurons are regulated in the face of such abnormal code scripts, and how development is affected during embryogenesis and the immediate postnatal period (2). Improving the classification of epilepsy genotypes will undoubtedly improve calculating sibling risk for epilepsy, and this, in turn, improves riskassessment accuracy and facilitates genetic counseling. However, most idiopathic epilepsies are complex genetic diseases; they occur most frequently in relatives of individuals (3), yet do not exhibit a simple Mendelian pattern, for multiple genes seem to be simultaneously involved, and a diversity of "susceptible" genes collaborate in determining risk (2) This article reviews recent progress in molecular genetics of epilepsy.

Decreased cortical inhibition and yet cerebellar pathology in ‘familial cortical myoclonic tremor with epilepsy’

“…Alternatively, both the cerebellar pathology and the changes in cortical SICI result from a common mechanism, for instance a channelopathy. Channelopathies have been related to other epilepsy syndromes as well as SCA6 32–35. This is also in line with the observation that HV, which changes blood pH leading to membrane instability, induces DBN in FCMTE and SCA6, and not in healthy controls.…”

Familial cortical myoclonic tremor with epilepsy: A single syndromic classification for a group of pedigrees bearing common features

“…Several monogenic epilepsy syndromes are caused by mutations in genes encoding (subunits of) ion channels, and FCMTE also is hypothesized to be a channelopathy 30–32. The pathological findings showed striking similarities with SCA‐6 and Rocker mice 33–36.…”

Relationship Between Migraine and Epilepsy in Pediatric Age

“…Epilepsy results from an abnormal electrical discharge in neuronal cells and any alteration of ion membrane permeability or ion exchange activity may lead to recurrent spontaneous seizures 11,12 . While different types of epilepsy have been associated with mutations in human genes encoding subunits of voltage‐gated Na and K channels, 25–27 the pathogenesis of migraine is probably less understood.…”