title: The genetics of Dravet syndrome.
abstract: Dravet syndrome (DS), otherwise known as severe myoclonic epilepsy of infancy (SMEI), is an epileptic encephalopathy presenting in the first year of life. DS has a genetic etiology: between 70% and 80% of patients carry sodium channel α1 subunit gene (SCN1A) abnormalities, and truncating mutations account for about 40% and have a significant correlation with an earlier age of seizures onset. The remaining SCN1A mutations comprise splice-site and missense mutations, most of which fall into the pore-forming region of the sodium channel. Mutations are randomly distributed across the SCN1A protein. Most mutations are de novo, but familial SCN1A mutations also occur. Somatic mosaic mutations have also been reported in some patients and might explain the phenotypical variability seen in some familial cases. SCN1A exons deletions or chromosomal rearrangements involving SCN1A and contiguous genes are also detectable in about 2-3% of patients. A small percentage of female patients with a DS-like phenotype might carry PCDH19 mutations. Rare mutations have been identified in the GABARG2 and SCN1B genes. The etiology of about 20% of DS patients remains unknown, and additional genes are likely to be implicated.
authors.affiliation: Pediatric Neurology Unit and Laboratories, Children's Hospital A Meyer - University of Florence, Florence, Italy. c.marini@meyer.it
authors.forename: Carla
authors.initials: C
authors.lastname: Marini
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.forename: Arvid
authors.initials: A
authors.lastname: Suls
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
mesh_terms: D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels