Abstracts

Rationale: Dravet syndrome is an SCN1A mutation-related, infantile onset epilepsy syndrome. Cognitive impairment in Dravet syndrome is well recognized, but little is known about adaptive profiles. Methods: Adaptive function of 61 patients with Dravet syndrome was analyzed with a parental form questionnaire of Adaptive Behavior Assessment System-II (ABAS-II). Patients over the age of 4 had more in-depth analysis of multiple variables related to seizure severity, seizure types, antiepileptic medications and therapeutic interventions as related to ABAS-II scores. Results: 26 boys and 35 girls were included. Mean age at the time of the test was 5 ± 3.7 years old (Median = 4; IQR = 2 - 6.5). General adaptive composite (GAC) score (66 ± 21) decreased with age (r = -0.564, p < 0.0001), and correlated well with Full-scale intelligence quotient (FSIQ, 51 ± 16) (r = 0.628, p = 0.003). Subjects demonstrated a strength in socialization (76 ± 21), and a weakness in practical skills (64 ± 20) (p = 0.002). Of the 34 subjects who were 4 years or older at the time of the test, only 7(20%) had GAC score of 70 or higher. Developmental concern was less likely to be noticed by the parents before age 2 in this group (1/7 vs. 19/27, p = 0.007). In addition, therapeutic interventions were more likely to be initiated prior to any noted developmental delays (4/7 vs. 4/27, p = 0.03). However, on the contrary, nearly half of the subjects (8/14) who were developmentally normal at age 2, showed delayed adaptive behavioral skills after 4 years of age. Of the 34 subjects who were older than 4, 19 patients scored 50 or less in GAC score. These severely affected subjects were more likely to have mutations in the sensor (S4), pore (S5, S6) or in L3 coding regions (5/15 vs. 0/12, p = 0.027). These children were also diagnosed later (median = 4 years old, IQR = 2 - 9 vs. median = 2, IQR = 1 - 6, p = 0.025) and none of them had early initiation of therapeutic interventions (0/18 vs. 8/13, p = 0.001). Interestingly neither seizure frequency or medication variables correlated to subsequent adaptive outcome, although there was a trend for children who had status epilepticus to have GAC scores of less than 50. Conclusions: Adaptive behavior skills were significantly delayed in Dravet syndrome with a relative strength in socialization. Our findings suggest that multiple factors can influence adaptive function, including the specific type of gene mutation. Early diagnosis and therapies may enhance adaptive skills.