Abstracts

Rationale: Rationale: Dravet syndrome (DS) is an aggressive epileptic encephalopathy. Pharmacoresistant seizures of several types plague most DS patients throughout life. Gait difficulties are a common, but inconsistent finding. The majority of cases are caused by mutations in the SCN1A gene, but little information is available about how particular mutations influence the adult phenotype. The purpose of this study is to correlate different types of SCN1A mutations and (1) seizure control, (2) occurrence of convulsive status epilepticus (cSE), and (3) the presence of crouch gait in adult patients. Methods: Methods: In a cohort of 10 adult patients with DS caused by SCN1A mutations, we investigated seizure frequency, history of cSE and gait. All patients were identified in the epilepsy clinic, between 2009 and 2011. SCN1A mutations were divided in 4 different groups based on location or effect of the mutation. Retrospective chart review and recent physical examination were completed in all cases. Results: Results: All patients had a pathogenic mutation in the SCN1A gene. Four SCN1A mutations have not been previously described. Greater than 90% seizure reduction was observed (compared to childhood frequency) in 6/7 patients with missense mutations in the pore forming region (PFR) of the Nav1.1 protein (group A) and nonsense mutations (group B). One patient with a splice-site mutation (group C) and another with a mutation outside the PFR (group D) became free of all types of seizures. cSE after the age of 19 years was observed in only 1 patient. Crouch gait, without spasticity, is identified as an element of the adult DS phenotype. However, only half of our adult DS cohort demonstrated crouch gait. This feature was observed in 5/7 patients from groups A and B and in no patients from groups C and D. Conclusions: Conclusion: This study shows that seizure control improves and cSE become less frequent in DS as patients age, independently of their SCN1A mutation type. Complete seizure freedom was seen in 2 patients (groups C and D). Finally, this study shows that in DS, crouch gait can be observed in up to 50% of adults with SCN1A mutation. Although no definite statistical correlations could be drawn due to the small number of patients, it is interesting to note that crouch gait was only observed in those patients with nonsense mutations or mutations in the PRF. Future studies with larger cohorts will be required to formally assess an association of gait abnormalities with particular SCN1A mutations.