title: The spectrum of SCN1A-related infantile epileptic encephalopathies.
abstract: The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.
authors.affiliation: Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, South Australia.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Harkin
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: McMahon
authors.forename: Xenia
authors.initials: X
authors.lastname: Iona
authors.forename: Leanne
authors.initials: L
authors.lastname: Dibbens
authors.forename: James T
authors.initials: JT
authors.lastname: Pelekanos
authors.forename: Sameer M
authors.initials: SM
authors.lastname: Zuberi
authors.forename: Lynette G
authors.initials: LG
authors.lastname: Sadleir
authors.forename: Eva
authors.initials: E
authors.lastname: Andermann
authors.forename: Deepak
authors.initials: D
authors.lastname: Gill
authors.forename: Kevin
authors.initials: K
authors.lastname: Farrell
authors.forename: Mary
authors.initials: M
authors.lastname: Connolly
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stanley
authors.forename: Michael
authors.initials: M
authors.lastname: Harbord
authors.forename: Frederick
authors.initials: F
authors.lastname: Andermann
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Sat Dev
authors.initials: SD
authors.lastname: Batish
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Jones
authors.forename: William K
authors.initials: WK
authors.lastname: Seltzer
authors.forename: Alison
authors.initials: A
authors.lastname: Gardner
authors.forename: Grant
authors.initials: G
authors.lastname: Sutherland
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004828:Epilepsies, Partial / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics*; D010290:Parents; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels