Clinical, molecular-genetic, and therapeutic characteristics of patients with Dravet syndrome: Initial results from a hospital-based registry

Objective. To present initial results from the hospital registry of patients with Dravet syndrome (DS) and to characterize the clinical, molecular-genetic, and therapeutic features of this cohort. Material and methods. This single-center retrospective observational study analyzed data from the hospital registry of Dravet syndrome at the Veltischev Research Clinical Institute of Pediatrics and Pediatric Surgery. The registry initially included 54 patients; after expert clinical and genetic review, 48 patients met the criteria for DS and constituted the primary analysis cohort. Results. More than 90% of patients were aged 3—17 years at enrollment. The mean age at disease onset was 5.4 months with median of 5 (3—7) months. In all cases, the initial symptom was epileptic seizures. The first seizures were either febrile or afebrile: afebrile seizures predominated in patients with onset at 5 months or younger, whereas febrile seizures predominated in those with onset at 6 months or older. Precipitating factors included fever associated with infection in 34 patients (71%), vaccination in 8 (17%), and bathing in hot water or overheating in 4 (8%). Hemiclonic and generalized tonic-clonic seizures were the most frequent seizure types. Status epilepticus occurred in 20 patients (42%): febrile in 7 (15%), convulsive in 11 (23%), and non-convulsive in 9 (19%). Intellectual developmental disorders were identified in 41 patients (85%), and autism spectrum disorders in 22 (46%), most frequently between ages 2 and 5 years. A genetically confirmed pathogenic or likely pathogenic variant in the SCN1A gene was identified in 46 patients (96% of the cohort, 98% of those examined). Loss of function variants were observed in 23 patients (50%), including nonsense variants, reading frameshift variants, and a large deletion of 2q24.3, all classified as pathogenic. Missense variants were found in 16 cases (35%), and splicing variants in 7 cases (15%). The median age at clinical diagnosis of DS was 24 [12—48] months, with a median diagnostic delay of 18 [8—36] months. Conclusions. This hospital registry provides the first systematic description of the clinical, molecular-genetic, and therapeutic characteristics of patients with DS In Russia. The diagnostic delay observed underscores ongoing challenges and the need for greater vigilance among pediatricians and neurologists.