Long-term cognitive outcomes in tuberous sclerosis complex

Abstract

Aim: To investigate the interdependence between risk factors associated with long-term intellectual development in individuals with tuberous sclerosis complex (TSC). Method: The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of individuals with TSC. In phase 1 of the study, baseline measures of intellectual ability, epilepsy, cortical tuber load, and mutation were obtained for 125 children (63 females, 62 males; median age=39mo). In phase 2, at an average of 8 years later, intellectual abilities were estimated for 88 participants with TSC and 35 unaffected siblings. Structural equation modelling was used to determine the risk pathways from genetic mutation through to IQ at phase 2. Results: Intellectual disability was present in 57% of individuals with TSC. Individuals without intellectual disability had significantly lower mean IQ compared to unaffected siblings, supporting specific genetic factors associated with intellectual impairment. Individuals with TSC who had a slower gain in IQ from infancy to middle childhood were younger at seizure onset and had increased infant seizure severity. Structural equation modelling indicated indirect pathways from genetic mutation, to tuber count, to seizure severity in infancy, through to IQ in middle childhood and adolescence. Interpretation: Early-onset and severe epilepsy in the first 2 years of life are associated with increased risk of long-term intellectual disability in individuals with TSC, emphasizing the importance of early and effective treatment or prevention of epilepsy. What this paper adds: Intellectual disability was present in 57% of individuals with tuberous sclerosis complex (TSC). Those with TSC without intellectual disability had significantly lower mean IQ compared to unaffected siblings. Earlier onset and greater severity of seizures in the first 2 years were observed in individuals with a slower gain in intellectual ability. Risk pathways through seizures in the first 2 years predict long-term cognitive outcomes in individuals with TSC.

Publication DOI: https://doi.org/10.1111/dmcn.14356
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences
College of Health & Life Sciences > Clinical and Systems Neuroscience
Funding Information: Members of the Tuberous Sclerosis 2000 Study Group are as follows: V Attard, A Clarke, FV Elmslie, AK Saggar, St George's Hospital, London; D Baines, BA Kerr, Royal Manchester Children's Hospital, Manchester; N Higgins, Department of Addenbrooke's Hospita
Additional Information: ©2019 The Authors.Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press. This is an open access article under the terms of the Creative Commons Attribution License, which permits use,distribution and reproduction in any medium, provided the original work is properly cited
Uncontrolled Keywords: Pediatrics, Perinatology, and Child Health,Developmental Neuroscience,Clinical Neurology
Publication ISSN: 1469-8749
Last Modified: 18 Mar 2024 08:33
Date Deposited: 06 Dec 2019 11:40
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://onlinel ... 1111/dmcn.14356 (Publisher URL)
PURE Output Type: Article
Published Date: 2020-03
Published Online Date: 2019-09-19
Accepted Date: 2019-08-02
Authors: , Tuberous Sclerosis 2000 Study Group

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