Severity of manifestations in tuberous sclerosis complex in relation to genotype

Epilepsia. 2014 Jul;55(7):1025-9. doi: 10.1111/epi.12680. Epub 2014 Jun 10.


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.

Keywords: Epilepsy; TSC mutations; Tuberous sclerosis complex.

MeSH terms

  • Adolescent
  • Adult
  • Belgium / epidemiology
  • Child
  • Child, Preschool
  • Databases, Factual / trends
  • Female
  • Genotype*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Retrospective Studies
  • Severity of Illness Index*
  • Tuberous Sclerosis / diagnosis*
  • Tuberous Sclerosis / genetics*
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / genetics*
  • United States / epidemiology
  • Young Adult


  • TSC2 protein, human
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins