The prevalence and risk factors for autism spectrum disorders (ASD) in a cohort of 103 patients with tuberous sclerosis complex (TSC) were determined in a study at the Massachusetts General Hospital, Boston, MA. ASD was diagnosed in 40% of patients with TSC. Patients with ASD were younger than those without ASD (9.9 vs 16.2 years, p<0.001), and had lower IQs (51 vs 81, p<0.001). Frequency of male gender was not significantly different (49% vs 42%) in patients with and without ASD, and skin, renal, cardiac, pulmonary, and ophthalmological manifestations were similar. TSC/ASD patients were less likely to have mutations in the TSC1 gene. They had an earlier onset of seizures (0.7 vs 2.9 years, p<0.002) and more frequent seizures, and a significantly greater amount of interictal epileptiform features, especially in the left temporal lobe (82% vs 61%, p<0.049). Infantile spasms occurred in 59% of TSC with ASD patients and 32% of TSC without ASD (p<0.014). On MRI, the regional distribution of tuber burden was unaltered, but patients with TSC2 and ASD had a higher prevalence of cyst-like tubers. [1]

COMMENT. Autistic spectrum disorders are characterized by impaired social interaction, restricted interests, and repetitive behaviors. Risk of ASD development in children with TSC is increased with early persistent seizure activity in the left temporal lobe, the brain region responsible for social perception and communication. Interictal epileptiform discharges in the temporal lobe, and cyst-like tubers on MRI may provide markers for ASD in TSC.

Commonly missed signs of TSC, and presenting symptoms and signs according to age group are reported from the Massachusetts General Hospital study of 243 patients with TSC [2]. Average age at diagnosis was 7.5 years, 81% before age 10 years (range, birth to 73 years). The most common presenting features were new onset seizures, infantile spasms, family history of TSC, cardiac rhabdomyomas, and hypopigmented macules. Missed symptoms and signs, most commonly seizures (including infantile spasms) and dermatological signs, were reported in 39% of patients. Patients with a TSC2 genetic mutation were diagnosed on average 9 years before patients with a TSC1 mutation, and were more likely to present with infantile spasms, developmental delay, or angiofibromas. Patients with a TSC1 mutation were more likely to present with a family history of TSC or hypopigmented macules. Patients with no mutation identified were more likely to present with renal angiomyolipomas. Infantile spasms are a risk factor for slow cognitive development in TSC. Immediate diagnosis of infantile spasms by EEG hypsarrhythmia and early treatment are required to reduce seizure frequency and risk of cognitive impairment. Vigabatrin is recommended for infantile spasms secondary to TSC.