title: Intellectual abilities in tuberous sclerosis complex: risk factors and correlates from the Tuberous Sclerosis 2000 Study.
abstract: BACKGROUND
  Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood.
  
  
  METHODS
  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.
authors.affiliation: MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry,The Institute of Psychiatry,Kings College London,London,UK.
authors.forename: P F
authors.initials: PF
authors.lastname: Bolton
authors.affiliation: MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry,The Institute of Psychiatry,Kings College London,London,UK.
authors.forename: M
authors.initials: M
authors.lastname: Clifford
authors.affiliation: MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry,The Institute of Psychiatry,Kings College London,London,UK.
authors.forename: C
authors.initials: C
authors.lastname: Tye
authors.affiliation: Department of Medical Genetics,University of Cambridge,Cambridge,UK.
authors.forename: C
authors.initials: C
authors.lastname: Maclean
authors.affiliation: Section of Developmental Psychiatry,University of Cambridge,Cambridge,UK.
authors.forename: A
authors.initials: A
authors.lastname: Humphrey
authors.affiliation: MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry,The Institute of Psychiatry,Kings College London,London,UK.
authors.forename: K
authors.initials: K
authors.lastname: le Maréchal
authors.affiliation: Department of Radiology,Addenbrooke's Hospital,Cambridge,UK.
authors.forename: J N P
authors.initials: JN
authors.lastname: Higgins
authors.affiliation: Institute of Child Health,University College London UK and National Centre for Young People with Epilepsy,Lingfield,UK.
authors.forename: B G R
authors.initials: BG
authors.lastname: Neville
authors.affiliation: MRC Centre for Social Genetic & Developmental Psychiatry & Department of Child Psychiatry,The Institute of Psychiatry,Kings College London,London,UK.
authors.forename: F
authors.initials: F
authors.lastname: Rijsdjik
authors.affiliation: Department of Medical Genetics,University of Cambridge,Cambridge,UK.
authors.forename: J R W
authors.initials: JR
authors.lastname: Yates
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000175:diagnosis*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007360:Intelligence; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013036:Spasms, Infantile / Q000150:complications*; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000523:psychology*; D006113:United Kingdom
keywords: Brain; IQ; cortical tuber; epilepsy; intelligence; tuberous sclerosis