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European Child & Adolescent Psychiatry

, Volume 16, Issue 1, pp 16–24 | Cite as

The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC)

A postal survey of UK families
  • Petrus J. de VriesEmail author
  • Ann Hunt
  • Patrick F. Bolton
ORIGINAL CONTRIBUTION

Abstract

Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder associated with a wide range of physical features and very high rates of numerous neurocognitive manifestations. However, there is great variability of expression of these features and understanding of the mechanisms underlying this variability is still limited. Mental retardation (MR) and male gender are known to be associated with increased risks of psychopathologies in the general population, but no study has examined these subgroups in TSC as possible contributors to the variable expression observed. It has also remained unclear whether familial-sporadic differences may contribute to variable expression. In this postal survey, UK families reported the frequency and range of physical and behavioural abnormalities in 265 children and adolescents with TSC. Analysis revealed no gender or familial-sporadic differences. Children with MR were significantly more likely to have an autism spectrum disorder, attention deficit-related symptoms and speech and language difficulties. They were more likely to have a history of epilepsy, facial angiofibromata and shagreen patches and tended to have a greater number of physical features of the disorder. However, about one third of the children without MR had features suggestive of a developmental disorder. Anxiety symptoms, depressed mood and aggressive outbursts occurred at equally high rates in those with and without MR. These findings show that TSC can place any child or adolescent at significantly increased risk of a range of neurodevelopmental disabilities. These difficulties, often not recognised, require significant clinical and research attention.

Keywords

autism spectrum disorders disruptive behaviour disorders behavioural phenotype cognition variability of expression 

Notes

Acknowledgements

This survey was undertaken with financial support from the Tuberous Sclerosis Association (TSA), a grant from the Hayward Foundation and the Anglia and Oxford NHS R&D fund. PdV was, in addition, supported by scholarships from the Raymond and Beverly Sackler Fund and the Cambridge Commonwealth Trust. The authors also thank Maria Boyiatzi for undertaking data entering, and Deborah McCartney and Prof. Christopher Howe for helpful comments on earlier drafts. This paper is dedicated to the memory of Janet Medcalf, who was Head of Support Services of the TSA at the time of the study.

References

  1. 1.
    American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (DSM-IV), 4th ed. American Psychiatric Association, Washington, DC Google Scholar
  2. 2.
    Bolton PF (2004) Neuro-epileptic correlates of autistic symptomatology in tuberous sclerosis. Ment Retard Dev Disabil Res Rev 10:126–131PubMedCrossRefGoogle Scholar
  3. 3.
    Bolton PF, Park RJ, Higgins JN, Griffiths PD, Pickles A (2002) Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 125:1247–1255PubMedCrossRefGoogle Scholar
  4. 4.
    Bolton PF, Griffiths PD (1997) Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 349(9049):392–395PubMedCrossRefGoogle Scholar
  5. 5.
    Clarke A, Cook P, Osborne JP (1996) Cranial computed tomographic findings in tuberous sclerosis are not affected by sex. Dev Med Child Neurol 38(2):139–145PubMedCrossRefGoogle Scholar
  6. 6.
    Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy Y, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ (2001) Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1 disease in multiple organs. Am J Hum Genet 68:64–80PubMedCrossRefGoogle Scholar
  7. 7.
    de Vries PJ, Bolton PF (2000) Genotype–phenotype correlations in Tuberous Sclerosis. J Med Genet 37:e3PubMedCrossRefGoogle Scholar
  8. 8.
    de Vries P, Humphrey A, McCartney D, Prather P, Bolton P, Hunt A, TSC Behaviour Consensus Panel (2005) Consensus clinical guidelines for the assessment of cognitive and behavioural problems in Tuberous Sclerosis. Eur Child Adolesc Psychiatry 14(4):183–190PubMedCrossRefGoogle Scholar
  9. 9.
    Emerson E (2003) Prevalence of psychiatric disorders in children and adolescents with and without intellectual disability. J Intellect Disabil Res 47(1):51–58PubMedCrossRefGoogle Scholar
  10. 10.
    Fombonne E (1999) The epidemiology of autism: a review. Psychol Med 29:769–786PubMedCrossRefGoogle Scholar
  11. 11.
    Gillberg IC, Gillberg C, Ahlsen G (1994) Autistic behaviour and attention deficits in tuberous sclerosis: a population-based study. Dev Med Child Neurol 36:50–56PubMedCrossRefGoogle Scholar
  12. 12.
    Goodman R (1997) The strengths and difficulties questionnaire: a research note. J Child Adolesc Psychopharmacol 38(5):581–586Google Scholar
  13. 13.
    Hunt A (1998) A comparison of the abilities, health and behaviour of 23 people with Tuberous Sclerosis and age 5 and as adults. J Appl Res Intellect Disabil 11(3):227–238CrossRefGoogle Scholar
  14. 14.
    Hunt A (1993) Development, behaviour and seizures in 300 cases of tuberous sclerosis. J Intellect Disabil Res 37(1):41–51PubMedCrossRefGoogle Scholar
  15. 15.
    Hunt A (1983) Tuberous sclerosis: a survey of 97 cases. III: Family aspects. Dev Med Child Neurol 25(3):353–357PubMedCrossRefGoogle Scholar
  16. 16.
    Hunt A, Dennis J (1987) Psychiatric disorder among children with tuberous sclerosis. Dev Med Child Neurol 29(2):190–198PubMedCrossRefGoogle Scholar
  17. 17.
    Hunt A, Shepherd C (1993) A prevalence study of autism in tuberous sclerosis. J Autism Dev Disord 23(2):323–339PubMedCrossRefGoogle Scholar
  18. 18.
    Joinson C, O’Callaghan FJ, Osborne JP, Martyn C, Harris T, Bolton PF (2003) Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med 33(2):334–344CrossRefGoogle Scholar
  19. 19.
    Jones AC, Daniells CE, Snell RG, Tachataki M, Idziaszczyk SA, Krawczak M, Sampson JR, Cheadle JP (1997) Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis. Hum Mol Genet 6(12):2155–2161PubMedCrossRefGoogle Scholar
  20. 20.
    Lewis JC, Thomas HV, Murphy KC, Sampson JR (2004) Genotype and psychological phenotype in tuberous sclerosis. J Med Genet 41: 203–207PubMedCrossRefGoogle Scholar
  21. 21.
    Lord C, Rutter M, Goode S, Heemsbergen J, Jordan H, Mawhood L, Schopler E (1989) Autism diagnostic observation schedule: a standardised observation of communication and social behavior. J Autism Dev Disord 19(2):185–212CrossRefGoogle Scholar
  22. 22.
    Lord C, Rutter M, Le Couteur A (1994) Autism diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24:659–685CrossRefGoogle Scholar
  23. 23.
    Meltzer H, Gatward R, Goodman R, Ford T (2000) Mental health of children and adolescents in Great Britain. The Stationery Office, LondonGoogle Scholar
  24. 24.
    O’Callaghan F (1999) Tuberous sclerosis. Br Med J 318(7190):1019–1020Google Scholar
  25. 25.
    O’Callaghan F, Noakes M, Osborne JP (2000) Renal angiomyolipomata and learning difficulty in tuberous sclerosis complex. J Med Genet 37:156–157PubMedCrossRefGoogle Scholar
  26. 26.
    Pickles A, Starr E, Kazak S, Bolton P, Papanicolaou K, Bailey A, Goodman R, Rutter M (2000) Variable expression of the autism broader phenotype: findings from extended pedigrees. J Child Psychol Psychiatry 41(4):491–502PubMedCrossRefGoogle Scholar
  27. 27.
    Povey S, Burley MW, Attwood J, Benham F, Hunt D, Jeremiah SJ, Franklin D, Gillett G, Malas S, Robson EB, Tippett P, Edwards JH, Kwaitkowski DJ, Super M, Mueller R, Fryer A, Clarke A, Webb D, Osborne J (1994) Two loci for tuberous sclerosis: one on 9q34 and one on 16p13. Ann Hum Genet 58(2):107–127PubMedGoogle Scholar
  28. 28.
    Prather P, de Vries PJ (2004) Behavioral and cognitive aspects of tuberous sclerosis complex. J Child Neurol 19(9):666–674PubMedGoogle Scholar
  29. 29.
    Raven J (1956) Coloured progressive matrices. Oxford Psychologists Press, OxfordGoogle Scholar
  30. 30.
    Roach E, Gomez M, Northrup H (1998) Tuberous Sclerosis consensus conference: revised diagnostic criteria. J Child Neurol 13(12):624–628PubMedGoogle Scholar
  31. 31.
    Smalley SL, Burger F, Smith M (1994) Phenotypic variation of tuberous sclerosis in a single extended kindred. J Med Genet 31(10):761–765PubMedCrossRefGoogle Scholar
  32. 32.
    Webb DW, Fryer AE, Osborne JP (1996) Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol 38(2):146–155PubMedCrossRefGoogle Scholar
  33. 33.
    Wechsler D (1992) Wechsler intelligence scale for children—third edition, UK. The Psychological Corporation Limited, LondonGoogle Scholar
  34. 34.
    World Health Organisation (1992) The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organisation, Geneva, p 362Google Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2007

Authors and Affiliations

  • Petrus J. de Vries
    • 1
    Email author
  • Ann Hunt
    • 2
  • Patrick F. Bolton
    • 3
  1. 1.Developmental Psychiatry SectionUniversity of CambridgeCambridgeUK
  2. 2.Tuberous Sclerosis AssociationNorth LeighUK
  3. 3.Institute of PsychiatryLondonUK

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