Incidence of Dravet Syndrome in a US Population

OBJECTIVE: De novo mutations of the gene sodium channel 1a (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. WHAT’S KNOWN ON THIS SUBJECT: De novo mutations of the sodium channel gene SCN1A are the major cause of Dravet syndrome, an infantileonset epileptic encephalopathy. The incidence of this genetic disorder in the United States is