The impact of genetic and experimental studies on classification and therapy of the epilepsies

Here we review the genetic epilepsies from the clinician perspective. A monogenic inheritance has been defined only in a minority of idiopathic epilepsies making improper to rename genetic the category of idiopathic epilepsies, until the presumptive multigenic mechanism will be demonstrated. A search for gene mutations must be done in any patient with candidate genetic types of epilepsy or epileptic/epileptogenic encephalopathy (e.g. familial forms) to complete the diagnostic process, define the prognosis and optimize the therapy. Advanced methods are available to express the gene variant in experimental model systems and test its effect on the properties of the affected protein, on neuronal excitability and on phenotypes in model organisms, and may help in identifying treatments with compatible action mechanisms. The influence of genetic studies on epilepsy taxonomy is now a matter of discussion: their impact on the international classification of the epilepsies will hopefully be defined soon.