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Intellectual abilities in tuberous sclerosis complex: risk factors and correlates from the Tuberous Sclerosis 2000 Study

Published online by Cambridge University Press:  01 April 2015

P. F. Bolton ,
M. Clifford ,
C. Tye ,
C. Maclean ,
A. Humphrey ,
K. le Maréchal ,
J. N. P. Higgins ,
B. G. R. Neville ,
F. Rijsdjik  and
J. R. W. Yates
...Show all authors
P. F. Bolton*
Affiliation:
MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry, The Institute of Psychiatry, Kings College London, London, UK
M. Clifford
Affiliation:
MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry, The Institute of Psychiatry, Kings College London, London, UK
C. Tye
Affiliation:
MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry, The Institute of Psychiatry, Kings College London, London, UK
C. Maclean
Affiliation:
Department of Medical Genetics, University of Cambridge, Cambridge, UK
A. Humphrey
Affiliation:
Section of Developmental Psychiatry, University of Cambridge, Cambridge, UK
K. le Maréchal
Affiliation:
MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry, The Institute of Psychiatry, Kings College London, London, UK
J. N. P. Higgins
Affiliation:
Department of Radiology, Addenbrooke's Hospital, Cambridge, UK
B. G. R. Neville
Affiliation:
Institute of Child Health, University College London UK and National Centre for Young People with Epilepsy, Lingfield, UK
F. Rijsdjik
Affiliation:
MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry, The Institute of Psychiatry, Kings College London, London, UK
J. R. W. Yates
Affiliation:
Department of Medical Genetics, University of Cambridge, Cambridge, UK East Anglian Medical Genetics Service, Addenbrooke's Hospital, Cambridge, UK
*
*Address for correspondence: P. F. Bolton, Professor of Child Psychiatry, MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry, The Institute of Psychiatry, Kings College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. The South London & Maudsley NHS Trust Biomedical Research Centre in Mental Health. (Email: [email protected])
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Abstract

Background

Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood.

Method

The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of the natural history of TSC. One hundred and twenty-five UK children age 0–16 years with TSC and born between January 2001 and December 2006 were studied. Intelligence was assessed using standardized measures at ≥2 years of age. The age of onset of epilepsy, the type of seizure disorder, the frequency and duration of seizures, as well as the response to treatment was assessed at interview and by review of medical records. The severity of epilepsy in the early years was estimated using the E-Chess score. Genetic studies identified the mutations and the number of cortical tubers was determined from brain scans.

Results

TSC2 mutations were associated with significantly higher cortical tuber count than TSC1 mutations. The extent of brain involvement, as indexed by cortical tuber count, was associated with an earlier age of onset and severity of epilepsy. In turn, the severity of epilepsy was strongly associated with the degree of intellectual impairment. Structural equation modelling supported a causal pathway from genetic abnormality to cortical tuber count to epilepsy severity to intellectual outcome. Infantile spasms and status epilepticus were important contributors to seizure severity.

Conclusions

The findings support the proposition that severe, early onset epilepsy may impair intellectual development in TSC and highlight the potential importance of early, prompt and effective treatment or prevention of epilepsy in tuberous sclerosis.

Keywords

Braincortical tuberepilepsyintelligenceIQtuberous sclerosis
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 11 , August 2015 , pp. 2321 - 2331
Copyright
Copyright © Cambridge University Press 2015 

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