European Child & Adolescent Psychiatry

, Volume 16, Issue 5, pp 305–308 | Cite as

Autism spectrum disorder and Klinefelter syndrome

  • P. Jha
  • D. Sheth
  • M. Ghaziuddin



Autism is a severe handicapping disorder of early childhood characterized by a distinct pattern of social and communication impairment with rigid ritualistic interests. In about 10–25% of cases, it is associated with known medical conditions. Population-based studies of autism have found that Klinefelter’s syndrome (KS), a common chromosome abnormality, is sometimes associated with autism. However, few detailed case descriptions of patients with KS and autism have not been published.

Case Report

In this paper, we describe the occurrence of autistic features in two cases of Klinefelter syndrome, one with the typical XXY karyotype and the other with the XXYY variant.


Autistic features may be more common in persons with Klinefelter syndrome than generally believed. We propose that all patients with KS should be screened for the presence of autism.


autism chromosomes klinefelter syndrome 


  1. 1.
    American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Washington, DC: AuthorGoogle Scholar
  2. 2.
    Bekaroglu M, Soylu C, Soylu N, Bilici M (1997) Bipolar affective disorder associated with Klinefelter’s syndrome–a case report. Isr J Psychiatry Relat Sci 34(4):308–310PubMedGoogle Scholar
  3. 3.
    Boone KB, Swerdloff RS, Miller BL, Geschwind DH, Razani J, Lee A, Gonzalo IG, Haddal A, Rankin K, Lu P, Paul L (2001) Neuropsychological profiles of adults with Klinefelter syndrome. Journal of the International Neuropsychology Society 7(4):446–456CrossRefGoogle Scholar
  4. 4.
    Borghgraef M, Fryns JP, Van den Berghe H (1991) The 48, XXYY syndrome. Follow-up data on clinical characteristics and psychological findings in 4 patients. Genet Couns 2(2):103–108PubMedGoogle Scholar
  5. 5.
    Eytan A, Paoloni-Giacobino A, Thorens G, Eugster N, Graf I (2002) Fire-setting behavior associated with Klinefelter syndrome. Int J Psychiatry Med 32(4):395–399PubMedGoogle Scholar
  6. 6.
    Friedrich U, Dalby M, StaehelinJensen T, et al. (1982) Chromosomal studies of children with developmental language retardation. Dev Med Child Neurol 24:645–652PubMedCrossRefGoogle Scholar
  7. 7.
    Geschwind DH, Gregg J, Boone K, et al. (1998) Klinefelter’s syndrome as a model of anomalous cerebral laterality: testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray. Dev Genet 23:215–229PubMedCrossRefGoogle Scholar
  8. 8.
    Geschwind DH, Boone KB, Miller BL, Swerdloff RS (2000) Neurobehavioral phenotype of Klinefelter Syndrome. Ment Retard Dev Disabil Res Rev 6:107–116PubMedCrossRefGoogle Scholar
  9. 9.
    Giedd JN, Clasen LS, Lenroot R, Greenstein D, Wallace GL, Ordaz S, Molloy EA, Blumenthal JD, Tossell JW, Stayer C, Samango-Sprouse CA, Shen D, Davatzikos C, Merke D, Chrousos GP (2006) Puberty-related influences on brain development. Mol Cell Endocrinol 254–255:154–162PubMedCrossRefGoogle Scholar
  10. 10.
    Hallmayer J, Hebert JM, Spiker D, Lotspeich L, McMahon WM, Petersen PB, Nicholas P, Pingree C, Lin AA, Cavalli-Sforza LL, Risch N, Ciaranello RD (1996) Autism and the X chromosome. Multipoint sib-pair analysis. Arch Gen Psychiatry 53(11):985–989PubMedGoogle Scholar
  11. 11.
    Harkulich JF, Marchner TJ, Brown EB (1979) Neurological, neuropsychological, and behavioral correlates of Klinefelter’s syndrome. J Nerv Ment Dis 167(6):359–363PubMedCrossRefGoogle Scholar
  12. 12.
    Jacobs PA, Hassold TJ, Whittington E, et al. (1988) Klinefelter’s syndrome: an analysis of the origin of the additional sex chromosome using molecular probes. Ann Hum Genet 52:93–109PubMedGoogle Scholar
  13. 13.
    Kielinen M, Rantala H, Timonen E, Linna SL, Moilanen I (2004) Associated medical disorders and disabilities in children with autistic disorder: a population-based study. Autism 8(1):49–60PubMedCrossRefGoogle Scholar
  14. 14.
    Lue Y, Jentsch JD, Wang C, Rao PN, Hikim AP, Salameh W, Swerdloff RS (2005) XXY mice exhibit gonadal and behavioral phenotypes similar to Klinefelter syndrome. Endocrinology 146(9):4148–4154PubMedCrossRefGoogle Scholar
  15. 15.
    Mandoki MG, Sumner GS, Hoffman RP, Riconda DL (1991) A review of Klinefelter’s syndrome in children and adolescents. J Am Acad Child Adolesc Psychiatry 30(2):167–172PubMedCrossRefGoogle Scholar
  16. 16.
    Merhar SL, Manning-Courtney P (2006) Two boys with 47, XXY and Autism. J Autism Dev Disord, DOI.10Google Scholar
  17. 17.
    Nielsen J, Sillesen I, Sorensen AM, Sorensen K (1979) Follow-up until age 4 to 8 of 25 unselected children with sex chromosome abnormalities, compared with sibs and controls. Birth Defects Orig Art Ser 15:15–73PubMedGoogle Scholar
  18. 18.
    Nielsen J, Wohlert M (1991) Sex chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Birth Defects Orig Art Ser 26:209–223Google Scholar
  19. 19.
    Ratcliffe SG, Butler GE, Jones M (1991) Edinburgh study of growth and development of children with sex chromosome abnormalities. IV. Birth Defects Orig Art Ser 26:1–44Google Scholar
  20. 20.
    Shen D, Liu D, Liu H, Clasen L, Giedd J, Davatzikos C (2004) Automated morphometric study of brain variation in XXY males. Neuroimage 23(2):648–653PubMedCrossRefGoogle Scholar
  21. 21.
    Skuse DH (2006) Sexual dimorphism in cognition and behaviour: the role of X-linked genes. Eur J Endocrinol 1(155 Suppl):S99–S106CrossRefGoogle Scholar
  22. 22.
    Talebizadeh Z, Bittel DC, Veatch OJ, Butler MG, Takahashi TN, Miles JH (2004) Do known mutations in neuroligin genes (NLGN3 and NLGN4) cause autism? J Autism Dev Disord 34(6):735–736PubMedCrossRefGoogle Scholar
  23. 23.
    Temple CM, Sanfilippo PM (2003) Executive skills in Klinefelter’s syndrome. Neuropsychologia 41(11):1547–1559PubMedCrossRefGoogle Scholar
  24. 24.
    van Rijn S, Swaab H, Aleman A, Kahn RS (2006) X Chromosomal effects on social cognitive processing and emotion regulation: a study with Klinefelter men (47,XXY). Schizophr Res 84(2–3):194–203PubMedCrossRefGoogle Scholar
  25. 25.
    Vincent JB, Melmer G, Bolton PF, Hodgkinson S, Holmes D, Curtis D, Gurling HM (2005) Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region. Psychiatr Genet 15(2):83–90PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag 2007

Authors and Affiliations

  1. 1.Division of Child PsychiatryUniversity of Michigan HospitalAnn ArborUSA

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