Abstract
SummaryTuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by mutations in TSC1 or TSC2. Epilepsy occurs in 80%‐90% of affected individuals during their lifetime, and up to one‐third of children with TSC will develop epileptic (infantile) spasms, for which vigabatrin has been shown to be particularly effective. Epilepsy severity and epileptic spasms are consistent markers of risk for the development of intellectual impairment in TSC. Although previous studies demonstrate a bimodal distribution of intellectual ability in TSC, recent findings suggest a unimodal distribution, which may reflect a change in IQ distribution over time. We compared 3 large historical UK cohorts of TSC (n = 331) that show varied distributions of intellectual ability, first ruling out differences in study methodology. Later‐born individuals had a higher frequency of reported spasms and higher likelihood of vigabatrin administration, but were less likely to have profound intellectual impairment, compared to the earlier‐born individuals. Our findings suggest that epileptic spasms went undetected in the older patients and therefore were not treated, leading to a higher occurrence of profound impairment, whereas the later born cohort had better access to treatment. These findings support the importance of early identification and treatment of seizures in TSC.
Highlights
Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by a mutation of TSC1 or TSC2 and characterized
There were some differences in the modes of ascertainment between the 3 studies, these differences cannot explain the differences observed in IQ distribution across cohorts
Within the subset of individuals with severe to profound disability, there was no significant difference across cohorts by sex, reported age of seizure onset, history of spasms, or type of mutation (TSC1 versus TSC2; all p > 0.05)
Summary
We directly compare and combine findings from 3 cohorts of TSC: 1. 1995, age = 4.0–75.0 years, M:F = 1:0.9) was ascertained through a 1998 census in the Wessex area of SW England.[10] The average reported age at seizure onset was 28.6 months and 47% of the sample had a history of epileptic spasms. Data were not available for the proportion that received vigabatrin treatment. Assessment of intellectual ability was conducted using the Wechsler Adult Intelligence Scale (WAIS-R), Wechsler Intelligence Scale for Children (WISC-III), Raven’s Coloured Progressive Matrices, or Vineland Adaptive Behavior Scale. Estimated IQ was bimodally distributed, with a skewness of À0.14 and a kurtosis of À1.51; 55.5% had IQ in the normal range, 14% had mild to severe impairments, and 30.5% had profound disability
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