title: Incidence of Dravet Syndrome in a US Population.
abstract: OBJECTIVE
  De novo mutations of the gene sodium channel 1α (SCN1A) are the major cause of Dravet syndrome, an infantile epileptic encephalopathy. US incidence of DS has been estimated at 1 in 40 000, but no US epidemiologic studies have been performed since the advent of genetic testing.
  
  
  METHODS
  In a retrospective, population-based cohort of all infants born at Kaiser Permanente Northern California during 2007-2010, we electronically identified patients who received ≥2 seizure diagnoses before age 12 months and who were also prescribed anticonvulsants at 24 months. A child neurologist reviewed records to identify infants who met 4 of 5 criteria for clinical Dravet syndrome: normal development before seizure onset; ≥2 seizures before age 12 months; myoclonic, hemiclonic, or generalized tonic-clonic seizures; ≥2 seizures lasting >10 minutes; and refractory seizures after age 2 years. SCN1A gene sequencing was performed as part of routine clinical care.
  
  
  RESULTS
  Eight infants met the study criteria for clinical Dravet syndrome, yielding an incidence of 1 per 15 700. Six of these infants (incidence of 1 per 20 900) had a de novo SCN1A missense mutation that is likely to be pathogenic. One infant had an inherited SCN1A variant that is unlikely to be pathogenic. All 8 experienced febrile seizures, and 6 had prolonged seizures lasting >10 minutes by age 1 year.
  
  
  CONCLUSIONS
  Dravet syndrome due to an SCN1A mutation is twice as common in the United States as previously thought. Genetic testing should be considered in children with ≥2 prolonged febrile seizures by 1 year of age.
authors.affiliation: Departments of Neurology and Pediatrics, University of California, San Francisco, San Francisco, California; wuy@ucsf.edu.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Departments of Neurology and Pediatrics, University of California, San Francisco, San Francisco, California;
authors.forename: Joseph
authors.initials: J
authors.lastname: Sullivan
authors.affiliation: Divisions of Child Neurology.
authors.forename: Sharon S
authors.initials: SS
authors.lastname: McDaniel
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Meisler
authors.affiliation: Research, and.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Walsh
authors.affiliation: Research, and.
authors.forename: Sherian Xu
authors.initials: SX
authors.lastname: Li
authors.affiliation: Research, and Neonatology, Kaiser Permanente Northern California, Oakland, California; and.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kuzniewicz
mesh_terms: D002140:California / Q000453:epidemiology; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human