Children diagnosed with tuberous sclerosis antenatally/ before seizures-are they a less severe group of patients?

Abstract

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant condition caused by mutations in the TSC1 or TSC2 gene with a birth incidence of 1 in 6,000. TSC is associated with variable neuro developmental outcomes, seizures and benign tumours in various organs. In most cases, the diagnosis is made after seizures have occurred. Approximately 17% are diagnosed antenatally. Neurodevelopment outcome is linked to seizure severity. Trials aimed at improving outcome with early use of vigabatrin and mTOR inhibitors are underway. Early diagnosis of TSC, preferably prior to seizure onset, will be needed to maximize benefit. Aim/Methods: Retrospective medical records review of all TSC patients born between 2001 and 2015 who were seen in the TSC clinic at Sydney Children's Hospital. We compared those diagnosed pre- and postseizure to determine if a pre-seizure TSC diagnosis results in better long-term neurodevelopmental outcome. Results: 74 patients were ascertained: 34 diagnosed pre-seizure (21 antenatally), 40 diagnosed post-seizure. (1) Of those diagnosed pre-seizure, 77% presented with cardiac rhabdomyoma(s). (2) 72% of the pre-seizure cohort developed clinical seizures-53% by 12 months of age, compared with 87% of the post-seizure cohort. (3) 47% of the pre-seizure patients had developmental disability (DD) compared with 68% of the post- seizure patients (p = .027). Conclusion: (1) Pre-seizure TSC cases have a milder clinical course with less severe DD and fewer seizures. (2) Fetuses/children with cardiac rhabdomyomas ought to be assessed for possible diagnosis of TSC. 3. Pre-seizure TSC infants need active management to identify onset of seizures and provide early treatment.L6124786972016-10-07 <br />