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

被引:48
作者
Bolton, P. F. [1 ,2 ]
Clifford, M. [1 ,2 ]
Tye, C. [1 ,2 ]
Maclean, C. [3 ]
Humphrey, A. [4 ]
le Marechal, K. [1 ,2 ]
Higgins, J. N. P. [5 ]
Neville, B. G. R. [6 ,7 ]
Rijsdjik, F. [1 ,2 ]
Yates, J. R. W. [3 ,8 ]
机构
[1] Kings Coll London, MRC, Ctr Social Genet & Dev Psychiat, London SE5 8AF, England
[2] Kings Coll London, Inst Psychiat, Dept Child Psychiat, London SE5 8AF, England
[3] Univ Cambridge, Dept Med Genet, Cambridge, England
[4] Univ Cambridge, Sect Dev Psychiat, Cambridge, England
[5] Addenbrookes Hosp, Dept Radiol, Cambridge CB2 2QQ, England
[6] Univ Coll London UK, Inst Child Hlth, Lingfield, England
[7] Natl Ctr Young People Epilepsy, Lingfield, England
[8] Addenbrookes Hosp, East Anglian Med Genet Serv, Cambridge, England
关键词
Brain; cortical tuber; epilepsy; intelligence; IQ; tuberous sclerosis; AUTISM SPECTRUM DISORDERS; MENTAL-RETARDATION; EPILEPSY SEVERITY; INFANTILE SPASMS; DEFICITS; DISABILITY; EVEROLIMUS; SEIZURES; COUNT; ONSET;
D O I
10.1017/S0033291715000264
中图分类号
B849 [应用心理学];
学科分类号
040203 ;
摘要
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.
引用
收藏
页码:2321 / 2331
页数:11
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