title: Genetic mutations associated with status epilepticus.
abstract: This paper reports the results of a preliminary search of the literature aimed at identifying the genetic mutations reported to be strongly associated with status epilepticus. Genetic mutations were selected for inclusion if status epilepticus was specifically mentioned as a consequence of the mutation in standard genetic databases or in a case report or review article. Mutations in 122 genes were identified. The genetic mutations identified were found in only rare conditions (sometimes vanishingly rare) and mostly in infants and young children with multiple other handicaps. Most of the genetic mutations can be subdivided into those associated with cortical dysplasias, inborn errors of metabolism, mitochondrial disease, or epileptic encephalopathies and childhood syndromes. There are no identified 'pure status epilepticus genes'. The range of genes underpinning status epilepticus differs in many ways from the range of genes underpinning epilepsy, which suggests that the processes underpinning status epilepticus differ from those underpinning epilepsy. It has been frequently postulated that status epilepticus is the result of a failure of 'seizure termination mechanisms', but the wide variety of genes affecting very diverse biochemical pathways identified in this survey makes any unitary cause unlikely. The genetic influences in status epilepticus are likely to involve a wide range of mechanisms, some related to development, some to cerebral energy production, some to diverse altered biochemical pathways, some to transmitter and membrane function, and some to defects in networks or systems. The fact that many of the identified genes are involved with cerebral development suggests that status epilepticus might often be a system or network phenomenon. To date, there are very few genes identified which are associated with adult-onset status epilepticus (except in those with preexisting neurological damage), and this is disappointing as the cause of many adult-onset status epilepticus cases remains obscure. It has been suggested that idiopathic adult-onset status epilepticus might often have an immunological cause but no gene mutations which relate to immunological mechanisms were identified. Overall, the clinical utility of what is currently known about the genetics of status epilepticus is slight and the findings have had little impact on clinical treatment despite what has been a very large investment in money and time. New genetic technologies may result in the identification of further genes, but if the identified genetic defects confer only minor susceptibility, this is unlikely to influence therapy. It is also important to recognize that genetics has social implications in a way that other areas of science do not. This article is part of a Special Issue entitled "Status Epilepticus".
authors.affiliation: UCL Institute of Neurology, University College London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bhatnagar
authors.affiliation: UCL Institute of Neurology, University College London, UK. Electronic address: s.shorvon@ucl.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Shorvon
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D012640:Seizures / Q000175:diagnosis / Q000235:genetics; D013226:Status Epilepticus / Q000175:diagnosis* / Q000235:genetics*
keywords: Cerebral dysplasia; Epileptic encephalopathy; Genetics; Inborn errors of metabolism; Mitochondrial disease; Status epilepticus