Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Klinefelter syndrome presenting as behavioral problems in a young adult


Background An 18-year-old Somali man presented to a primary care clinic to investigate a potential pathophysiological reason for behavioral problems at school that had arisen in the past 1–2 years. A previous physical examination at school revealed the patient to have small, firm testicles which prompted further testing.

Investigation Thyroid function and levels of prolactin, total testosterone, follicle-stimulating hormone and luteinizing hormone were determined. Testes were measured. Chromosome analysis testing was performed to determine the patient's karyotype.

Diagnosis Klinefelter syndrome with a 47,XXY karyotype.

Management Testosterone replacement therapy was recommended, but the patient declined treatment.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Lanfranco, F., Kamischke, A., Zitzmann, M. & Nieschlag, E. Klinefelter's syndrome. Lancet 364, 273–283 (2004).

    CAS  Article  PubMed  Google Scholar 

  2. 2

    Tyler, C. & Edman, J. C. Down syndrome, Turner syndrome, and Klinefelter syndrome: primary care throughout the life span. Prim. Care 31, 627–648 (2004).

    Article  PubMed  Google Scholar 

  3. 3

    Bojesen, A., Juul, S. & Gravholt, C. H. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J. Clin. Endocrinol. Metab. 88, 622–626 (2003).

    CAS  Article  PubMed  Google Scholar 

  4. 4

    Visootsak, J. & Graham, J. M. Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J. Rare Dis. 1, 42 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5

    Bojesen, A. & Gravholt, C. H. Klinefelter syndrome in clinical practice. Nat. Clin. Pract. Urol. 4, 192–204 (2007).

    Article  PubMed  Google Scholar 

  6. 6

    Amory, J. K., Anawalt, B. D., Paulsen, C. A. & Bremner, W. J. Klinefelter's syndrome. Lancet 356, 333–335 (2000).

    CAS  Article  PubMed  Google Scholar 

  7. 7

    Smyth, C. M. & Bremner, W. J. Klinefelter syndrome. Arch. Intern. Med. 158, 1309–1314 (1998).

    CAS  Article  PubMed  Google Scholar 

  8. 8

    Wikstrom, A. M. & Dunkel, L. Testicular function in Klinefelter syndrome. Horm. Res. 69, 317–326 (2008).

    CAS  PubMed  Google Scholar 

  9. 9

    Boada, R., Janusz, J., Hutaff-Lee, C. & Tartaglia, N. The cognitive phenotype in Klinefelter syndrome: a review of the literature including genetic and hormonal factors. Dev. Disabil. Res. Rev. 15, 284–294 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10

    Manning, M. A. & Hoyme, H. E. Diagnosis and management of the adolescent boy with Klinefelter syndrome. Adolesc. Med. 13, 367–374, viii (2002).

    PubMed  Google Scholar 

  11. 11

    Jha, P., Sheth, D. & Ghaziuddin, M. Autism spectrum disorder and Klinefelter syndrome. Eur. Child Adolesc. Psychiatry 16, 305–308 (2007).

    CAS  Article  PubMed  Google Scholar 

  12. 12

    Paduch, D. A., Fine, R. G., Bolyakov, A. & Kiper, J. New concepts in Klinefelter syndrome. Curr. Opin. Urol. 18, 621–627 (2008).

    Article  PubMed  Google Scholar 

  13. 13

    Boks, M. P. et al. Psychiatric morbidity and X-chromosomal origin in a Klinefelter sample. Schizophr. Res. 93, 399–402 (2007).

    Article  PubMed  Google Scholar 

  14. 14

    van Rijn, S., Aleman, A., Swaab, H. & Kahn, R. Klinefelter's syndrome (karyotype 47,XXY) and schizophrenia-spectrum pathology. Br. J. Psychiatry 189, 459–460 (2006).

    Article  PubMed  Google Scholar 

  15. 15

    van Rijn, S. et al. What it is said versus how it is said: comprehension of affective prosody in men with Klinefelter (47,XXY) syndrome. J. Int. Neuropsychol. Soc. 13, 1065–1070 (2007).

    Article  PubMed  Google Scholar 

  16. 16

    van Rijn, S., Swaab, H., Aleman, A. & Kahn, R. S. Social behavior and autism traits in a sex chromosomal disorder: Klinefelter (47XXY) syndrome. J. Autism Dev. Disord. 38, 1634–1641 (2008).

    Article  PubMed  Google Scholar 

  17. 17

    Bojesen, A., Juul, S., Birkebaek, N. H. & Gravholt, C. H. Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J. Clin. Endocrinol. Metab. 91, 1254–1260 (2006).

    CAS  Article  PubMed  Google Scholar 

  18. 18

    Bruining, H., Swaab, H., Kas, M. & van Engeland, H. Psychiatric characteristics in a self-selected sample of boys with Klinefelter syndrome. Pediatrics 123, e865–e870 (2009).

    Article  PubMed  Google Scholar 

  19. 19

    Ross, J. L. et al. Cognitive and motor development during childhood in boys with Klinefelter syndrome. Am. J. Med. Genet. A 146A, 708–719 (2008).

    Article  PubMed  Google Scholar 

  20. 20

    Kubler, A., Schulz, G., Cordes, U., Beyer, J. & Krause, U. The influence of testosterone substitution on bone mineral density in patients with Klinefelter's syndrome. Exp. Clin. Endocrinol. 100, 129–132 (1992).

    CAS  Article  PubMed  Google Scholar 

  21. 21

    Leichtnam, M. L., Rolland, H., Wuthrich, P. & Guy, R. H. Testosterone hormone replacement therapy: state of the-art and emerging technologies. Pharm. Res. 23, 1117–1132 (2006).

    CAS  Article  PubMed  Google Scholar 

  22. 22

    Beg, S., Al-Khoury, L. & Cunningham, G. R. Testosterone replacement in men. Curr. Opin. Endocrinol. Diabetes Obes. 15, 364–370 (2008).

    CAS  Article  PubMed  Google Scholar 

  23. 23

    Terzoli, G., Lalatta, F., Lobbiani, A., Simoni, G. & Colucci, G. Fertility in a 47,XXY patient: assessment of biological paternity by deoxyribonucleic acid fingerprinting. Fertil. Steril. 58, 821–822 (1992).

    CAS  Article  PubMed  Google Scholar 

  24. 24

    Schiff, J. D. et al. Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome. J. Clin. Endocrinol. Metab. 90, 6263–6267 (2005).

    CAS  Article  PubMed  Google Scholar 

  25. 25

    Bojesen, A., Juul, S., Birkebaek, N. & Gravholt, C. H. Increased mortality in Klinefelter syndrome. J. Clin. Endocrinol. Metab. 89, 3830–3834 (2004).

    CAS  Article  PubMed  Google Scholar 

  26. 26

    Brinton, L. A., Carreon, J. D., Gierach, G. L., McGlynn, K. A. & Gridley, G. Etiologic factors for male breast cancer in the U. S. Veterans Affairs medical care system database. Breast Cancer Res. Treat. 119, 185–192 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Campbell, W. A. & Price, W. H. Venous thromboembolic disease in Klinefelter's syndrome. Clin. Genet. 19, 275–280 (1981).

    CAS  Article  PubMed  Google Scholar 

  28. 28

    De Morentin, H. M., Dodiuk-Gad, R. P. & Brenner, S. Klinefelter's syndrome presenting with leg ulcers. Skinmed 3, 274–278 (2004).

    Article  PubMed  Google Scholar 

  29. 29

    Calvano Kuchler, E., De Andrade Risso, P., De Castro Costa, M., Modesto, A. & Vieira, A. R. Assessing the proposed association between tooth agenesis and taurodontism in 975 paediatric subjects. Int. J. Paediatr. Dent. 18, 231–234 (2008).

    Article  PubMed  Google Scholar 

  30. 30

    Schulman, G. S. et al. Taurodontism and learning disabilities in patients with Klinefelter syndrome. Pediatr. Dent. 27, 389–394 (2005).

    PubMed  Google Scholar 

Download references


The authors would like to thank the GIM RISE group at Harborview Medical Center. Written consent for publication was obtained from the patient. C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Author information




All authors researched the data for the article, provided a substantial contribution to discussions of the content, contributed equally to writing the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Alexandra M. Molnar.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Molnar, A., Terasaki, G. & Amory, J. Klinefelter syndrome presenting as behavioral problems in a young adult. Nat Rev Endocrinol 6, 707–712 (2010).

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing