Conference Coverage

Study delineates spectrum of Dravet syndrome phenotypes



Initial presentations of Dravet syndrome often differ from the prototypical phenotype, researchers said at the annual meeting of the American Epilepsy Society. About half of patients have an afebrile seizure as their first seizure, and it is common for patients to present with seizures before age 5 months. Patients also may have seizure onset after age 18 months, said Wenhui Li, a researcher affiliated with Children’s Hospital of Fudan University in Shanghai and University of Melbourne, and colleagues.

“Subtle differences in Dravet syndrome phenotypes lead to delayed diagnosis,” the researchers said. “Understanding key features within the phenotypic spectrum will assist clinicians in evaluating whether a child has Dravet syndrome, facilitating early diagnosis for precision therapies.”

Typically, Dravet syndrome is thought to begin with prolonged febrile hemiclonic or generalized tonic-clonic seizures at about age 6 months in normally developing infants. Multiple seizure types occur during subsequent years, including focal impaired awareness, bilateral tonic-clonic, absence, and myoclonic seizures.

Patients often do not receive a diagnosis of Dravet syndrome until they are older than 3 years, after “developmental plateau or regression occurs in the second year,” the investigators said. “Earlier diagnosis is critical for optimal management.”

To outline the range of phenotypes, researchers analyzed the clinical histories of 188 patients with Dravet syndrome and pathogenic SCN1A variants. They excluded from their analysis patients with SCN1A-positive genetic epilepsy with febrile seizures plus (GEFS+).

In all, 53% of the patients were female, and 2% had developmental delay prior to the onset of seizures. Age at seizure onset ranged from 1.5 months to 21 months (median, 5.75 months). Three patients had seizure onset after age 12 months, the authors noted.

In cases where the first seizure type could be classified, 52% had generalized tonic-clonic seizures at onset, 37% had hemiclonic seizures, 4% myoclonic seizures, 4% focal impaired awareness seizures, and 0.5% absence seizures. In addition, 1% had hemiclonic and myoclonic seizures, and 2% had tonic-clonic and myoclonic seizures.

Fifty-four percent of patients were febrile during their first seizure, and 46% were afebrile.

Status epilepticus as the first seizure occurred in about 44% of cases, while 35% of patients had a first seizure duration of 5 minutes or less.

The researchers had no disclosures.

SOURCE: Li W et al. AES 2019. Abstract 2.116.

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