Journal of Autism and Developmental Disorders

, Volume 44, Issue 2, pp 310–320 | Cite as

The Social Behavioral Phenotype in Boys and Girls with an Extra X Chromosome (Klinefelter Syndrome and Trisomy X): A Comparison with Autism Spectrum Disorder

  • Sophie van Rijn
  • Lex Stockmann
  • Martine Borghgraef
  • Hilgo Bruining
  • Conny van Ravenswaaij-Arts
  • Lutgarde Govaerts
  • Kerstin Hansson
  • Hanna Swaab
Original Paper
First Online:

Abstract

The present study aimed to gain more insight in the social behavioral phenotype, and related autistic symptomatology, of children with an extra X chromosome in comparison to children with ASD. Participants included 60 children with an extra X chromosome (34 boys with Klinefelter syndrome and 26 girls with Trisomy X), 58 children with ASD and 106 controls, aged 9 to 18 years. We used the Autism Diagnostic Interview, Social Responsiveness Scale, Social Anxiety Scale and Social Skills Rating System. In the extra X group, levels of social dysfunction and autism symptoms were increased, being in between controls and ASD. In contrast to the ASD group, the extra X group showed increased social anxiety. The effects were similar for boys and girls with an extra X chromosome.

Keywords

Klinefelter Trisomy X Autism Social functioning X chromosome Sex chromosomal aneuploidies 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was supported by a VENI grant (Grant Number 016.095.060 to SvR) from the Netherlands Organization for Scientific Research (NWO).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Achenbach, T. M. (1991). Manual for the Child Behaviour Checklist/4–18 and 1991 profile. Burlington, VT: University of Vermont Department of Psychiatry.Google Scholar
  2. A.P.A. (1994). Diagnostic and statistical manual of mental disorders IV (4th ed.). Washington, DC: American Psychiatric Association Press.Google Scholar
  3. Bearden, C. E., Reus, V. I., & Freimer, N. B. (2004). Why genetic investigation of psychiatric disorders is so difficult. Current Opinion in Genetics & Development, 14, 280.CrossRefGoogle Scholar
  4. Bender, B. G., Harmon, R. J., Linden, M. G., Bucher-Bartelson, B., & Robinson, A. (1999). Psychosocial competence of unselected young adults with sex chromosome abnormalities. American Journal of Medical Genetics-Neuropsychiatric Genetics, 88, 200–206.PubMedCrossRefGoogle Scholar
  5. Bishop, D. V., et al. (2011). Autism, language and communication in children with sex chromosome trisomies. Archives of Disease in Childhood, 10, 954–959. doi: 10.1136/adc.2009.179747.CrossRefGoogle Scholar
  6. Boada, R., Janusz, J., Hutaff-Lee, C., & Tartaglia, N. (2009). The cognitive phenotype in Klinefelter syndrome: A review of the literature including genetic and hormonal factors. Developmental Disabilities Research Reviews, 15, 284–294.PubMedCentralPubMedCrossRefGoogle Scholar
  7. Boone, K. B., et al. (2001). Neuropsychological profiles of adults with Klinefelter syndrome. Journal of International Neuropsychological Society, 7, 446–456.CrossRefGoogle Scholar
  8. Bruining, H., Swaab, H., Kas, M., & Van Engeland, H. (2009). Psychiatric characteristics in a self-selected sample of boys with klinefelter syndrome. Pediatrics, 123, e865–e870.PubMedCrossRefGoogle Scholar
  9. Bruining, H., et al. (2010). Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. PLoS One, 5, 7. doi: 10.1371/journal.pone.0010887.CrossRefGoogle Scholar
  10. Constantino, J. N., & Gruber, C. P. (2005). The social responsiveness scale. Los Angeles: Western Psychological Services.Google Scholar
  11. Constantino, J. N., et al. (2003). Validation of a brief quantitative measure of autistic traits: Comparison of the social responsiveness scale with the autism diagnostic interview-revised. Journal of Autism and Developmental Disorders, 33, 427.PubMedCrossRefGoogle Scholar
  12. Cox, A., et al. (1999). Autism spectrum disorders at 20 and 42 months of age: Stability of clinical and ADI-R diagnosis. Journal of Child Psychology and Psychiatry, 40, 719–732. doi: 10.1017/s002196309900400x.PubMedCrossRefGoogle Scholar
  13. Dekking, Y. M. (1983). [Handleiding sociale angst schaal voor kinderen] Manual social anxiety scale for children. Lisse, The Netherlands: Swets & Zeitlinger.Google Scholar
  14. Evers, A., Van Vliet-Mulder, J. C., & Ter Laak, J. (1992). Amsterdam. The Netherlands: Van Gorcum.Google Scholar
  15. Geschwind, D. H., & Dykens, E. (2004). Neurobehavioral and psychosocial issues in Klinefelter syndrome. Learning Disabilities Research & Practice, 19, 166–173. doi: 10.1111/j.1540-5826.2004.00100.x.CrossRefGoogle Scholar
  16. Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry, 160, 636–645.PubMedCrossRefGoogle Scholar
  17. Gresham, F. M., & Elliott, S. N. (1990). Social skills rating system manual. Circle Pines, MN: American Guidance Service.Google Scholar
  18. Harmon, R. J., Bender, B. G., Linden, M. G., & Robinson, A. (1998). Transition from adolescence to early adulthood: Adaptation and psychiatric status of women with 47, XXX. Journal of the American Academy of Child and Adolescent Psychiatry, 37, 286–291.PubMedCrossRefGoogle Scholar
  19. Hofmann, S. G. (2005). Perception of control over anxiety mediates the relation between catastrophic thinking and social anxiety in social phobia. Behaviour Research and Therapy, 43, 885–895. doi: 10.1016/j.brat.2004.07.002.PubMedCrossRefGoogle Scholar
  20. Konstantareas, M. M., & Homatidis, S. (1999). Chromosomal abnormalities in a series of children with autistic disorder. Journal of Autism and Developmental Disorders, 29, 275–285.PubMedCrossRefGoogle Scholar
  21. Leggett, V., Jacobs, P., Nation, K., Scerif, G., & Bishop, D. V. M. (2010). Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a systematic review. Developmental Medicine and Child Neurology, 52, 119–129. doi: 10.1111/j.1469-8749.2009.03545.x.PubMedCentralPubMedCrossRefGoogle Scholar
  22. Maner, J. K., & Kenrick, D. T. (2010). When adaptations go awry: Functional and dysfunctional aspects of social anxiety. Social Issues and Policy Review, 4, 111–142.PubMedCentralPubMedCrossRefGoogle Scholar
  23. Otter, M., Schrander-Stumpel, C., & Curfs, L. M. G. (2010). Triple X syndrome: A review of the literature. European Journal of Human Genetics, 18, 265–271. doi: 10.1038/ejhg.2009.109.PubMedCrossRefGoogle Scholar
  24. Palmen, S., et al. (2005). Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder. Psychological Medicine, 35, 561–570. doi: 10.1017/s0033291704003496.PubMedCrossRefGoogle Scholar
  25. Ratcliffe, S. (1999). Long-term outcome in children of sex chromosome abnormalities. Archives of Disease in Childhood, 80, 192–195.PubMedCrossRefGoogle Scholar
  26. Ratcliffe, S., Butler, G. E., & Jones, M. (1991). Edinburgh study of growth and development of children with sex chromosome abnormalities. IV. Birth Defects: Original Articles Series, 26, 1–44.Google Scholar
  27. Robinson, A., Bender, B., Linden, M., & Salbenblatt, J. (1991). Sex chromosome aneuploidy: The Denver prospective study. Birth Defects: Original Articles Series, 26, 59–115.Google Scholar
  28. Scourfield, J., Martin, N., Lewis, G., & McGuffin, P. (1999). Heritability of social cognitive skills in children and adolescents. British Journal of Psychiatry, 175, 559–564.PubMedCrossRefGoogle Scholar
  29. Sparks, B. F., et al. (2002). Brain structural abnormalities in young children with autism spectrum disorder. Neurology, 59, 184–192.PubMedCrossRefGoogle Scholar
  30. Stewart, D., Bailey, J., Netley, C., & Park, E. (1991). Growth, development and behavioral outcome from mid-adolescence to adulthood in subjects with chromosome aneuploidy: the Toronto study. Birth Defects: Original Articles Series, 26, 131–188.Google Scholar
  31. Tartaglia, N., Cordeiro, L., Howell, S., Wilson, R., & Janusz, J. (2010a). The spectrum of the behavioral phenotype in boys and adolescents 47, XXY (Klinefelter syndrome). Pediatric Endocrinology Reviews: PER, 8(Suppl 1), 151–159.PubMedCentralPubMedGoogle Scholar
  32. Tartaglia, N. R., Howell, S., Sutherland, A., Wilson, R., & Wilson, L. (2010b). A review of trisomy X (47, XXX). Orphanet Journal of Rare Diseases, 5, 9. doi: 10.1186/1750-1172-5-8.CrossRefGoogle Scholar
  33. van Rijn, S., Aleman, A., Swaab, H., Krijn, T., Vingerhoets, G., & Kahn, R. (2007). What it is said versus how it is said: comprehension of affective prosody in men with Klinefelter (47, XXY) syndrome. Journal of International Neuropsychological Society, 13, 1065–1070. doi: 10.1017/S1355617707071044.Google Scholar
  34. van Rijn, S., Swaab, H., Aleman, A., & Kahn, R. S. (2006). X Chromosomal effects on social cognitive processing and emotion regulation: A study with Klinefelter men (47, XXY). Schizophrenia Research, 84, 194–203. doi: 10.1016/j.schres.2006.02.020.PubMedCrossRefGoogle Scholar
  35. van Rijn, S., Swaab, H., Aleman, A., & Kahn, R. S. (2008). Social behavior and autism traits in a sex chromosomal disorder: Klinefelter (47XXY) syndrome. Journal of Autism and Developmental Disorders, 38, 1634–1641. doi: 10.1007/s10803-008-0542-1.PubMedCrossRefGoogle Scholar
  36. van’t Wout, M., van Rijn, S., Jellema, T., Kahn, R. S., & Aleman, A. (2009). Deficits in implicit attention to social signals in schizophrenia and high risk groups: Behavioural evidence from a new illusion. PloS one, 4, e5581. doi: 10.1371/journal.pone.0005581.CrossRefGoogle Scholar
  37. Visootsak, J., & Graham, J. M. (2009). Social function in multiple X and Y chromosome disorders: XXY, XYY, XXYY, XXXY. Developmental Disabilities Research Reviews, 15, 328–332.PubMedCrossRefGoogle Scholar
  38. Zechner, U., Wilda, M., Kehrer-Sawatzki, H., Vogel, W., Fundele, R., & Hameister, H. (2001). A high density of X-linked genes for general cognitive ability: A run-away process shaping human evolution? Trends in Genetics, 17, 697–701. doi: 10.1016/S0168-9525(01)02446-5.

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sophie van Rijn
    • 1
    • 2
  • Lex Stockmann
    • 1
    • 3
  • Martine Borghgraef
    • 4
  • Hilgo Bruining
    • 5
  • Conny van Ravenswaaij-Arts
    • 6
  • Lutgarde Govaerts
    • 7
  • Kerstin Hansson
    • 8
  • Hanna Swaab
    • 1
    • 2
  1. 1.Clinical Child and Adolescent StudiesLeiden UniversityLeidenThe Netherlands
  2. 2.Leiden Institute for Brain and CognitionLeidenThe Netherlands
  3. 3.Autism Center RivierduinenLeidenThe Netherlands
  4. 4.Center for Human GeneticsUniversity Hospital of LeuvenLeuvenBelgium
  5. 5.Department of Psychiatry, University Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
  6. 6.Department of Genetics, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
  7. 7.Department of Clinical GeneticsErasmus Medical CenterRotterdamThe Netherlands
  8. 8.Department of Clinical Genetics, LDGALeiden University Medical CenterLeidenThe Netherlands

Personalised recommendations