title: When should clinicians order genetic testing for Dravet syndrome?
abstract: The role of neuronal voltage-gated sodium channel, α-1 subunit (SCN1A) gene mutations in Dravet syndrome is well-established. With a broader phenotype than initially described, some patients lack features of Dravet syndrome as defined by the International League Against Epilepsy. We evaluated the predictive value of International League Against Epilepsy criteria for a positive mutation in a cohort of consecutively tested children. Mutations of SCN1A were evident in 16 of 69 children. Exhibiting ≥4 International League Against Epilepsy criteria demonstrated 100% sensitivity. Seven criteria (resistance to multiple antiepileptic drugs, multiple seizure types, abnormal electroencephalogram features, exacerbation with hyperthermia, normal development before seizure onset, seizures beginning before age 1 year, and psychomotor retardation) were present in ≥85% of mutation-positive cases. The three criteria that best predicted a mutation in SCN1A included exacerbation with hyperthermia, normal development before seizure onset, and the appearance of ataxia, pyramidal signs, or interictal myoclonus. We have demonstrated a high-sensitivity testing strategy for detecting mutations of SCN1A in children with suspected Dravet syndrome.
authors: Division of Pediatric Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. jamiekcapal@gmail.com
authors: Jamie K
authors: JK
authors: Fountain-Capal
authors: Katherine D
authors: KD
authors: Holland
authors: Donald L
authors: DL
authors: Gilbert
authors: Barbara E
authors: BE
authors: Hallinan
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010819:Physician's Role; D012189:Retrospective Studies; 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