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Individuals with TSC1 and TSC2 mutations show distinct patterns of intellectual abilities [Oral presentation abstract]

Wong, H. T., McCartney, Deborah L., Lewis, Julia, Sampson, Julian Roy, Howe, C. J. and De Vries, P. J. 2011. Individuals with TSC1 and TSC2 mutations show distinct patterns of intellectual abilities [Oral presentation abstract]. Journal of Intellectual Disability Research 55 (10) , p. 955. 10.1111/j.1365-2788.2011.01474_2.x

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Background: Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder associated with mutations in either TSC1 or TSC2. In contrast to the normal IQ distribution in the general population (Mean = 100, Standard deviation (SD) = 15), 30% of individuals with TSC are profoundly impaired (‘P phenotype’, IQ < 20) while the remaining 70% are normally distributed, with the mean IQ shifted downward (‘ND phenotype’). Genotype-phenotype studies to date have concluded that TSC2 is ‘more severe’ than TSC1. However, only two studies have utilized standardized measures of intelligence; both had signifi cant limitations. The fi rst study was very ‘categorical’, simply comparing impaired vs non-impaired IQ in TSC1 vs TSC2 mutations; the second used a range of neuropsychological measures but collapsed them into a composite score of unknown neurocognitive signifi cance. Here we examined the cognitive performance associated with TSC1 and TSC2 mutations. Methods: We studied a total sample of 100 individuals with TSC. The majority were from a sequentially ascertained sample for molecular genetics studies at the Institute of Medical Genetics, Cardiff University. The remaining subjects were identifi ed for a separate study in Cambridge, UK. All had intellectual assessments using hierarchical measurements to capture a best estimate IQ score, and detailed mutational analysis. Results: Of the overall sample (TSC1 = 26; TSC2 = 74) 72% of individuals fell in the normal distribution and 28% showed the P phenotype (TSC1 = 3; TSC2 = 25), essentially identical to the populationbased TSC expectation. When P phenotype individuals were excluded, those with TSC1 mutations had IQs indistinguishable from the general population (mean = 97.5; SD = 19.1). In contrast, IQs of those with TSC2 mutations had signifi cantly lower mean and wider standard deviation (mean = 71.6; SD = 27.1; TSC1 vs TSC2 p < 0.001). No gender-specifi c effects were observed. Conclusion: TSC1 and TSC2 clearly present with distinct patterns of intellectual abilities. The majority of individuals with TSC1 fall on a normal distribution identical to the general population and ∼10% have profound intellectual disability. In contrast, a substantial proportion of TSC2 mutations (34%) are associated with profound intellectual disability, and the remainder show a pattern of IQ signifi cantly more variable and shifted to the left than in TSC1 or the general population. Our results suggest that differences in the functional consequences of individual mutations should be explored further as predictors and determinants of the intellectual manifestations of TSC.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Tuberous Sclerosis Complex; Cognitive assessment; TSC1 mutation; TSC2 mutation
Additional Information: Conference item- presented at SSBP Annual Scientific Meeting
Publisher: Blackwell Publishing
ISSN: 0964-2633
Last Modified: 06 Feb 2022 11:52

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