Long-term cognitive outcomes in tuberous sclerosis complex

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalDevelopmental Medicine and Child Neurology
Early online date19 Sep 2019
DOIs
Publication statusE-pub ahead of print - 19 Sep 2019

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Tuberous Sclerosis
Intellectual Disability
Seizures
Aptitude
Siblings
Epilepsy
Mutation
Longitudinal Studies
Prospective Studies

Bibliographical note

©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

Cite this

@article{79820c58787049c685c3bab0be20444c,
title = "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.",
author = "Charlotte Tye and Mcewen, {Fiona S.} and Holan Liang and Lisa Underwood and Emma Woodhouse and Barker, {Edward D.} and Fintan Sheerin and Yates, {John R.W.} and Bolton, {Patrick F.} and N. Higgins and V. Attard and A. Clarke and Elmslie, {F. V.} and Saggar, {A. K.} and D. Baines and Kerr, {B. A.} and C. Brayne and I. Carcani-Rathwell and C. Connolly and M. Clifford and A. Lydon and F. Oluwo and H. Rogers and C. Srivastava and J. Steenbruggen and Cook, {J. A.} and C. Falconer and Davies, {D. M.} and Sampson, {J. R.} and Fryer, {A. E.} and M. Haslop and Y. Granader and Griffiths, {P. D.} and A. Hunt and Lam, {W. W.K.} and Kingswood, {J. C.} and Miedzybrodzka, {Z. H.} and H. Crawford and Morrison, {P. J.} and O'Callaghan, {F. J.K.} and Philip, {S. G.} and S. Seri and R. Sheehan-Dare and Shepherd, {C. H.}",
note = "{\circledC}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",
year = "2019",
month = "9",
day = "19",
doi = "10.1111/dmcn.14356",
language = "English",
journal = "Developmental Medicine and Child Neurology",
issn = "0012-1622",
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Long-term cognitive outcomes in tuberous sclerosis complex. /.

In: Developmental Medicine and Child Neurology, 19.09.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term cognitive outcomes in tuberous sclerosis complex

AU - Tye, Charlotte

AU - Mcewen, Fiona S.

AU - Liang, Holan

AU - Underwood, Lisa

AU - Woodhouse, Emma

AU - Barker, Edward D.

AU - Sheerin, Fintan

AU - Yates, John R.W.

AU - Bolton, Patrick F.

AU - Higgins, N.

AU - Attard, V.

AU - Clarke, A.

AU - Elmslie, F. V.

AU - Saggar, A. K.

AU - Baines, D.

AU - Kerr, B. A.

AU - Brayne, C.

AU - Carcani-Rathwell, I.

AU - Connolly, C.

AU - Clifford, M.

AU - Lydon, A.

AU - Oluwo, F.

AU - Rogers, H.

AU - Srivastava, C.

AU - Steenbruggen, J.

AU - Cook, J. A.

AU - Falconer, C.

AU - Davies, D. M.

AU - Sampson, J. R.

AU - Fryer, A. E.

AU - Haslop, M.

AU - Granader, Y.

AU - Griffiths, P. D.

AU - Hunt, A.

AU - Lam, W. W.K.

AU - Kingswood, J. C.

AU - Miedzybrodzka, Z. H.

AU - Crawford, H.

AU - Morrison, P. J.

AU - O'Callaghan, F. J.K.

AU - Philip, S. G.

AU - Seri, S.

AU - Sheehan-Dare, R.

AU - Shepherd, C. H.

N1 - ©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

PY - 2019/9/19

Y1 - 2019/9/19

N2 - 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.

AB - 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.

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