title: Genetic epilepsy syndromes without structural brain abnormalities: clinical features and experimental models.
abstract: Research in genetics of epilepsy represents an area of great interest both for clinical purposes and for understanding the basic mechanisms of epilepsy. Most mutations in epilepsies without structural brain abnormalities have been identified in ion channel genes, but an increasing number of genes involved in a diversity of functional and developmental processes are being recognized through whole exome or genome sequencing. Targeted molecular diagnosis is now available for different forms of epilepsy. The identification of epileptogenic mutations in patients before epilepsy onset and the possibility of developing therapeutic strategies tested in experimental models may facilitate experimental approaches that prevent epilepsy or decrease its severity. Functional analysis is essential for better understanding pathogenic mechanisms and gene interactions. In vitro experimental systems are either cells that usually do not express the protein of interest or neurons in primary cultures. In vivo/ex vivo systems are organisms or preparations obtained from them (e.g., brain slices), which should better model the complexity of brain circuits and actual pathophysiological conditions. Neurons differentiated from induced pluripotent stem cells generated from the skin fibroblasts of patients have recently allowed the study of mutations in human neurons having the genetic background of a given patient. However, there is remarkable complexity underlying epileptogenesis in the clinical dimension, as reflected by the fact that experimental models have not provided yet results having clinical translation and that, with a few exceptions concerning rare conditions, no new curative treatment has emerged from any genetic finding in epilepsy.
authors.affiliation: Pediatric Neurology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Viale Pieraccini 24, 50139, Florence, Italy, r.guerrini@meyer.it.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Carla
authors.initials: C
authors.lastname: Marini
authors.forename: Massimo
authors.initials: M
authors.lastname: Mantegazza
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D007473:Ion Channels