Tuberous Sclerosis 2000 Study Group (2020). Long-term cognitive outcomes in tuberous sclerosis complex. Developmental Medicine and Child Neurology, 62 (3), pp. 322-329.
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 |
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| 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 Hospital, Cambridge University Hospitals NHS Trust, Cambridge; C Brayne, Institute of Public Health, University of Cambridge; I Carcani‐Rathwell, C Connolly, M Clifford, A Lydon, F Oluwo, H Rogers, C Srivastava, J Steenbruggen, Institute of Psychiatry, Psychology & Neuroscience, King's College London; JA Cook, Sheffield Children's Hospital, Sheffield; C Falconer, St James's University Hospital, Leeds; DM Davies, JR Sampson, Institute of Medical Genetics, Cardiff; AE Fryer, Alder Hey Children's Hospital, Liverpool; M Haslop, Y Granader, University of Cambridge (currently Yeshiva University, New York); PD Griffiths, University of Sheffield; A Hunt, Tuberous Sclerosis Association, London; WWK Lam, Western General Hospital, Edinburgh; JC Kingswood, Royal Sussex County Hospital, Brighton; ZH Miedzybrodzka, College of Life Sciences and Medicine, Aberdeen; H Crawford, PJ Morrison, Belfast City Hospital; FJK O'Callaghan, Great Ormond Street Hospital/Institute of Child Health, University College London; SG Philip, Birmingham Children's Hospital, Birmingham; S Seri, Aston Brain Centre, School of Life and Health Sciences, Aston University, Birmingham; R Sheehan‐Dare, The General Infirmary, Leeds; CH Shepherd, Craigavon Area Hospital, Craigavon, UK. We wish to thank all of the families for their time and help with this study. This study was supported by grants awarded to PB from the Baily Thomas Charitable Fund, Tuberous Sclerosis Association, and Autism Speaks. CT was funded by a Medical Research Council studentship (G9817803), is currently a Tuberous Sclerosis Association Junior Fellow, and is supported by the National Institute for Health Research Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. The authors have no interests that might be perceived as posing a conflict or bias. |
| 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: | 20 Feb 2026 11:04 |
| Date Deposited: | 06 Dec 2019 11:40 |
| Full Text Link: | |
| Related URLs: |
https://www.sco ... ons/85073997273
(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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