Severity of manifestations in tuberous sclerosis complex in relation to genotype.

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) commonly present with significant neurologic deficits, including seizures, autism, and intellectual disability. Previous evidence suggests that the TSC2 mutation genotype may be associated with a more severe disease phenotype. This study evaluates the association of the TSC1 and TSC2 genotype with patient and disease characteristics in a retrospective review of a large TSC Natural History Database consisting of 919 patients with TSC.

METHODS: Univariate logistic regression was conducted to evaluate the association of the TSC1 and TSC2 gene mutations with patient and disease characteristics.

RESULTS: As compared to patients with the TSC1 mutation, patients with the TSC2 mutation were younger (p = 0.02), more likely to have partial epilepsy (odds ratio (OR) 1.74, p = 0.0015), complex partial seizures (OR 2.03, p = 0.02), infantile spasms (IS) (OR 1.67, p = 0.01), subependymal giant-cell astrocytomas (SEGAs) (OR 1.64, p = 0.01), and intellectual disability (OR 2.90, p = 0.0002).

SIGNIFICANCE: The clinical presentation of TSC is highly variable and not well understood. Our findings confirm and supplement existing literature that TSC2 mutation is likely to be associated with a more severe, earlier presenting TSC phenotype, including infantile spasms.