Mutations of Ion Channels in Genetic Epilepsies

© Springer International Publishing Switzerland 2015 P. Striano (ed.), Epilepsy Towards the Next Decade, Contemporary Clinical Neuroscience, DOI 10.1007/978-3-319-12283-0_2 M. Mantegazza () · R. Rusconi · S. Cestèle Institute of Molecular and Cellular Pharmacology (IPMC), CNRS UMR7275 and University of Nice-Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France e-mail: [email protected] Abstract Epileptogenic mutations have been identified in several ion channel genes, leading to the concept that several epilepsies can be considered channelopathies. However, increasing number of genes involved in a diversity of functional and developmental processes are being recognized through whole exome or genome sequencing, confirming that there is remarkable complexity underlying epileptogenesis. Additionally, recent studies of large cohorts of patients suggest that many patient-specific mutations in several genes are important for generating a particular phenotype, rather than mutations in a few genes common to most of the patients. We will review the epilepsy syndromes linked to ion channel gene mutations and the main results of genetic and functional studies, highlighting that also other genes can be important but stressing the central role of ion channels in the pathophysiology of genetic epilepsies. Although the picture is becoming more complex than previously thought, the identification of epileptogenic mutations in patients before epilepsy onset and the possibility to develop therapeutic strategies tested in experimental models may facilitate experimental approaches that prevent epilepsy or decrease its severity.