Abstracts

Rationale: To characterize the relationship between epilepsy and autism spectrum disorders in individuals with Tuberous Sclerosis Complex.Methods: We conducted a retrospective review of patients with Tuberous Sclerosis Complex (TSC) followed through the Carol and James Herscot Center for TSC at the Massachusetts General Hospital. Of the 260 patients seen, 87 were evaluated by one neuropsychologist and were of sufficient age to be evaluated for autism spectrum disorders (ASD). Data for those patients were evaluated, including history of epilepsy, refractory epilepsy, infantile spasms, and genotype.Results: Of the 87 TSC patients evaluated by a single neuropsychologist, 29 (33%) were found to have an ASD. Of those meeting criteria for ASD, 29 (100%) had a history of epilepsy, compared to 47 (81%) of individuals with TSC without ASD (p=0.013). Earlier age at onset of epilepsy was found in individuals with TSC and ASD (0.8 ± 0.7 yr vs. 3.1 ± 4.4 yr; p=0.001). Twenty-two (76%) of the individuals with TSC and ASD had a history of medically refractory epilepsy compared to 31 (53%) of individuals with TSC alone (p=0.043). Seventeen individuals (59%) with TSC and ASD had a history of infantile spasms compared to 18 (31%) individuals with TSC and no ASD (p=0.013). For this population of TSC individuals, ASD was not more common in male (TSC+ASD, 62% female, vs. TSC−ASD, 55% female, n.s.). Individuals with TSC and ASD had lower IQ than individuals with TSC alone (51.8 ± 28.9 vs. 78.5 ± 32.3; p<0.001). DNA mutational analysis was available in 78 of the 87 patients (90%), including 71 with a disease-causing mutation identified in the TSC1 or TSC2 gene. In the group with ASD, 3 individuals had a TSC1 mutation (14%), and 18 (86%) had a TSC2 mutation, while in the group without ASD, 21 (42%) had a TSC1 mutation and 29 (58%) had a TSC2 mutation (p=0.024).Conclusions: In our population, 1/3 of individuals with TSC met criteria for ASD. A history of epilepsy, early age of seizure onset, refractory epilepsy, a history of infantile spasms, and a TSC2 mutation are associated with increased risk of ASD in TSC.