NATIONAL HARBOR, MD—The incidence of Dravet syndrome in the US is double that of a prior estimate, according to research presented at the 2015 Child Neurology Society Annual Meeting. In addition, genetic testing should be considered in children who have two or more prolonged febrile seizures by age 12 months, researchers said. “Increased awareness of this disorder could lead to earlier diagnosis and, overall, to improved seizure control,” said Yvonne Wu, MD, MPH, a child neurologist and epidemiologist at the University of California, San Francisco.
Yvonne Wu, MD, MPH
The incidence of Dravet syndrome in the US had been estimated to be about 1 in 40,000 based on the National Collaborative Perinatal Project initiated in 1959. Of the 40,000 prospective births in that study, one baby developed Dravet syndrome. More recent studies in Europe looked at the incidence of Dravet syndrome due to SCN1A mutations. Those studies found that the incidence of the epileptic encephalopathy ranged from about one in 22,000 to one in 41,000.
To determine the incidence of Dravet syndrome in the US in the current era of genetic testing, Dr. Wu and colleagues studied a retrospective, population-based cohort of all infants born at Kaiser Permanente Northern California between January 1, 2007, and June 30, 2010. The investigators performed an electronic search for patients who received at least two diagnoses of seizure by age 12 months, and who still were prescribed anticonvulsants at age 24 months. The researchers then performed a detailed chart review to identify patients who met at least four of five criteria for clinical Dravet syndrome: children were normal prior to seizure onset; had at least two seizures, febrile or afebrile, by 12 months; had myoclonic, hemiclonic, or generalized tonic-clonic seizure type; had at least two prolonged seizures (ie, that lasted more than 10 minutes); and had refractory epilepsy requiring multiple anticonvulsants after age 24 months.
The investigators excluded patients who had epilepsy due to other reasons, such as brain malformation or tuberous sclerosis, and patients who had seizures prior to age 1 month.
The study population included 125,000 births. The investigators identified eight cases of clinical Dravet syndrome, yielding an incidence of one per 15,700. All eight patients obtained SCN1A genetic sequencing as part of their routine clinical care. Seven had a gene mutation identified, and the mutation was thought to be pathogenic in six of the cases.
Researchers may have missed cases if children with Dravet syndrome presented after 12 months or left Kaiser Permanente.
“There is some evidence, and hopefully there will be more over time, that making an earlier, correct diagnosis may lead to improved seizure control due to the use of more appropriate anticonvulsant therapies,” Dr. Wu said. “For instance, lamotrigine and carbamazepine should be avoided since they may exacerbate seizures, and other medications, such as stiripentol, topiramate, and valproate, may be more efficacious.” In addition, new therapies for Dravet syndrome may be on the horizon. Cannabidiol is in phase III trials, and a large trial of fenfluramine is planned, Dr. Wu said.
—Jake Remaly