Abstracts

Rationale: Dravet syndrome is a severe infantile onset epilepsy syndrome associated with mutations in the SCN1A gene encoding the alpha subunit of the voltage gated sodium channel Nav1.1. To date no large studies have systematically examined whether the phenotype of mutation negative patients differs from those who carry a SCN1A mutation.Methods: We prospectively evaluated 262 individuals with classical Dravet syndrome. 207 (79%) were SCN1A mutation positive and 55 (21%) were mutation negative. Mutation negative cases were tested for alternative diagnoses such as PCDH19, SLC2A1, STXBP1 and CDKL5 mutations. From structured referral data we examined a wide range of clinical characteristics including the epilepsy phenotype, seizure precipitants, EEG data, imaging studies, mutation class and response to medication.Results: SCN1A mutation negative patients presented with similar frequencies of prolonged febrile seizures, hemiclonic seizures, status epilepticus, focal seizures, myoclonic seizures and atypical absences. Equally, the onset of different seizure types was similar for both groups. There was no significant difference in seizure precipitants, evolution of EEG features or frequency of MRI abnormalities. Developmental status and associated comorbidities such as autistic features, behaviour problems and motor disorder did not differ between groups.Conclusions: We found no evidence that the phenotype of mutation negative Dravet syndrome patients was in any way different from those who carry a SCN1A mutation. Dravet syndrome remains a clinical diagnosis and all affected patients irrespective of mutation status should have access to appropriate treatment and therapies.