The Phenotypic Spectrum of Tuberous Sclerosis Complex: A Canadian Cohort

Abstract

OBJECTIVE We aimed to further elucidate the phenotypic spectrum of Tuberous Sclerosis Complex (TSC) depending on genotype. METHODS A retrospective review of patients seen in the TSC clinic at the Hospital for Sick Children was conducted and the frequency of TSC manifestations was compared based on genotype. RESULTS Nineteen-patients had TSC1 mutations, 36 had TSC2 mutations and 11 had no mutation identified (NMI). Patients with TSC2 mutations had a higher frequency of early-onset epilepsy and more frequent systemic manifestations. The NMI group had milder neurologic and systemic manifestations. Our data did not demonstrate that intellectual disability and infantile spasms were more common in TSC2 mutations. CONCLUSIONS This is the first Canadian pediatric cohort exploring the genotype-phenotype relationship in TSC. We report that some manifestations are more frequent and severe in TSC2 mutations and that NMI may have a milder phenotype. Disease surveillance and counseling should continue regardless of genotype until this is better elucidated.