Skip to main content
SpringerLink
Log in

Novel Approaches in the Management of Klinefelter Syndrome

  • Chapter
  • First Online:
Male Infertility

  • 2041 Accesses

Abstract

Klinefelter syndrome is the most common form of hypogonadism in men and is the leading genetic cause of male infertility. It also represents the most prevalent chromosomal aneuploidy in human beings. It is characterized by the presence of an extra X chromosome in a phenotypic male. The most abundant karyotype is 47, XXY, although other patterns including mosaicism (47, XY/47, XXY) and higher grade chromosomal aneuploidies containing supranumerous X chromosomes (48, XXXY, 49, XXXXY) are not uncommon. The latter phenotypes are more severely affected in terms of physical and mental development than men with classic 47, XXY karyotypes. The genetic cause is either from meiotic nondisjunction leading to failure of separation of the chromosome pair during the first or second division of gametogenesis or from mitotic nondisjunction in the developing zygote. Increasing maternal age has been reported to raise the risk of Klinefelter syndrome. The estimated prevalence of Klinefelter syndrome in men is 1:500 or 0.1–0.2% of the general population. However, extremely large discrepancies have been reported between prenatal and postnatal prevalence suggesting high rates of under diagnosis. A large Danish national registry study observed only 25% of the expected patients diagnosed after birth, and less than 10% of the expected diagnoses were made before puberty. Some of the major reasons for this underdiagnosis are thought to be the variable phenotype of Klinefelter syndrome and low awareness of the disease among medical professionals. Recognition of clinical features is hence important for early detection of this syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Klinefelter HF, Reifenstein EC, Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without Leydigism, increased, excretion of follicle stimulating hormone. J Clin Endocrinol Metab. 1942;2:615–27.

    Article  CAS  Google Scholar 

  2. Philip J, Lundsteen C, Owen D, Hirschhom K. The frequency of chromosome aberrations in tall men with special reference to 47, XYY and 47, XXY. Am J Hum Genet. 1976;28:404–11.

    PubMed  CAS  Google Scholar 

  3. Perwein E. Incidence of Klinefelter’s syndrome. In: Bandmann HJ, Breit R, editors. Klinefeleter’s syndrome. Berlin: Springer; 1984. p. 8–11.

    Chapter  Google Scholar 

  4. Samango-Sprouse C. Mental development in polysomy X Klinefelter syndrome (47, XXY; 48, XXXY): effects of incomplete X inactivation. Semin Reprod Med. 2001;19:193–202.

    Article  PubMed  CAS  Google Scholar 

  5. Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol. 1981;58:282–5.

    PubMed  CAS  Google Scholar 

  6. Bojesen A, Juul S, Hojbjerg Gravholt C. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003;88:622–6.

    Article  PubMed  CAS  Google Scholar 

  7. Robinson A, Lubs HA, Nielsen J, Sørensen K. Summary of clinical findings: profiles of children with 47, XXY, 47, XXX and 47, XYY karyotypes. Birth Defects Orig Artic Ser. 1979;15(1):261–6.

    PubMed  CAS  Google Scholar 

  8. Bojesen A, Gravholt CH. Klinefelter syndrome in clinical practice. Nat Clin Pract Urol. 2007;4(4):192–204.

    Article  PubMed  Google Scholar 

  9. Visootsak J, Aylstock M, Graham Jr JM. Klinefelter syndrome and its variants: an update and review for the primary pediatrician. Clin Pediatr (Phila). 2001;40(12):639–51.

    Article  CAS  Google Scholar 

  10. Aguirre D, Nieto K, Lazos M, Peña YR, Palma I, Kofman-Alfaro S, Queipo G. Extragonadal germ cell tumors are often associated with Klinefelter syndrome. Hum Pathol. 2006;37(4):477–80.

    Article  PubMed  CAS  Google Scholar 

  11. Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J Androl. 2003;24(1):41–8.

    PubMed  Google Scholar 

  12. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364(9430):273–83.

    Article  PubMed  CAS  Google Scholar 

  13. Paduch DA, Fine RG, Bolyakov A, Kiper J. New concepts in Klinefelter syndrome. Curr Opin Urol. 2008;18(6):621–7.

    Article  PubMed  Google Scholar 

  14. Campbell WA, Price WH. Venous thromboembolic disease in Klinefelter’s syndrome. Clin Genet. 1981;19(4):275–80.

    Article  PubMed  CAS  Google Scholar 

  15. Fricke GR, Mattern HJ, Schweikert HU, Schwanitz G. Klinefelter’s syndrome and mitral valve prolapse. An echocardiographic study in twenty-two patients. Biomed Pharmacother. 1984;38(2):88–97.

    PubMed  CAS  Google Scholar 

  16. Myhre SA, Ruvalcaba RH, Johnson HR, Thuline HC, Kelley VC. The effects of testosterone treatment in Klinefelter’s syndrome. J Pediatr. 1970;76(2):267–76.

    Article  PubMed  CAS  Google Scholar 

  17. Nielsen J, Pelsen B, Sørensen K. Follow-up of 30 Klinefelter males treated with testosterone. Clin Genet. 1988;33(4):262–9.

    Article  PubMed  CAS  Google Scholar 

  18. Lin YM, Huang WJ, Lin JS, Kuo PL. Progressive depletion of germ cells in a man with nonmosaic Klinefelter’s syndrome: optimal time for sperm recovery. Urology. 2004;63(2):380–1.

    Article  PubMed  Google Scholar 

  19. Wikström AM, Raivio T, Hadziselimovic F, Wikström S, Tuuri T, Dunkel L. Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion. J Clin Endocrinol Metab. 2004;89(5):2263–70.

    Article  PubMed  Google Scholar 

  20. Schiff JD, Palermo GD, Veeck LL, Goldstein M, Rosenwaks Z, Schlegel PN. Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab. 2005;90(11):6263–7.

    Article  PubMed  CAS  Google Scholar 

  21. Friedler S, Raziel A, Strassburger D, Schachter M, Bern O, Ron-El R. Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter’s syndrome. Hum Reprod. 2001;16(12):2616–20.

    Article  PubMed  CAS  Google Scholar 

  22. Madgar I, Dor J, Weissenberg R, Raviv G, Menashe Y, Levron J. Prognostic value of the clinical and laboratory evaluation in patients with nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy. Fertil Steril. 2002;77(6):1167–9.

    Article  PubMed  Google Scholar 

  23. Ramasamy R, Ricci JA, Palermo GD, Gosden LV, Rosenwaks Z, Schlegel PN. Successful fertility treatment for Klinefelter’s syndrome. J Urol. 2009;182(3):1108–13.

    Article  PubMed  CAS  Google Scholar 

  24. Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167(2 Pt 1):624–9.

    PubMed  CAS  Google Scholar 

  25. Staessen C, Tournaye H, Van Assche E, Michiels A, Van Landuyt L, Devroey P, Liebaers I, Van Steirteghem A. PGD in 47, XXY Klinefelter’s syndrome patients. Hum Reprod Update. 2003;9(4):319–30.

    Article  PubMed  CAS  Google Scholar 

  26. Hennebicq S, Pelletier R, Bergues U, Rousseaux S. Risk of trisomy 21 in offspring of patients with Klinefelter’s syndrome. Lancet. 2001;357(9274):2104–5.

    Article  PubMed  CAS  Google Scholar 

  27. Morel F, Bernicot I, Herry A, Le Bris MJ, Amice V, De Braekeleer M. An increased incidence of autosomal aneuploidies in spermatozoa from a patient with Klinefelter’s syndrome. Fertil Steril. 2003;79 Suppl 3:1644–6.

    Article  PubMed  Google Scholar 

  28. Levron J, Aviram-Goldring A, Madgar I, Raviv G, Barkai G, Dor J. Sperm chromosome analysis and outcome of IVF in patients with non-mosaic Klinefelter’s syndrome. Fertil Steril. 2000;74(5):925–9.

    Article  PubMed  CAS  Google Scholar 

  29. Izadyar F, Matthijs-Rijsenbilt JJ, den Ouden K, Creemers LB, Woelders H, de Rooij DG. Development of a cryopreservation protocol for type A spermatogonia. J Androl. 2002;23(4):537–45.

    PubMed  CAS  Google Scholar 

  30. Orwig KE, Schlatt S. Cryopreservation and transplantation of spermatogonia and testicular tissue for preservation of male fertility. J Natl Cancer Inst Monogr. 2005;34:51–6.

    Article  PubMed  Google Scholar 

  31. Nagano M, Patrizio P, Brinster RL. Long-term survival of human spermatogonial stem cells in mouse testes. Fertil Steril. 2002;78(6): 1225–33.

    Article  PubMed  Google Scholar 

  32. Sofikitis N. Transplantation of human spermatogonia into the seminiferous tubules (STs) of animal testicles results in the completion of the human meiosis and the generation of human motile spermatozoa. Fertil Steril. 1999;72 suppl 1:S83–4.

    Google Scholar 

  33. Patience C, Takeuchi Y, Weiss RA. Infection of human cells by an endogenous retrovirus of pigs. Nat Med. 1997;3(3):282–6.

    Article  PubMed  CAS  Google Scholar 

  34. Brinster RL, Zimmermann JW. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci USA. 1994;91(24): 11298–302.

    Article  PubMed  CAS  Google Scholar 

  35. Ogawa T. Spermatogonial transplantation technique in spermatogenesis research. Int J Androl. 2000;23 Suppl 2:57–9.

    Article  PubMed  Google Scholar 

  36. Honaramooz A, Snedaker A, Boiani M, Scholer H, Dobrinski I, Schlatt S. Sperm from neonatal mammalian testes grafted in mice. Nature. 2002;418(6899):778–81.

    Article  PubMed  CAS  Google Scholar 

  37. Schlatt S, Kim SS, Gosden R. Spermatogenesis and steroidogenesis in mouse, hamster and monkey testicular tissue after cryopreservation and heterotopic grafting to castrated hosts. Reproduction. 2002;124(3):339–46.

    Article  PubMed  CAS  Google Scholar 

  38. Oatley JM, de Avila DM, Reeves JJ, McLean DJ. Spermatogenesis and germ cell transgene expression in xenografted bovine testicular tissue. Biol Reprod. 2004;71(2):494–501.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Metabolism, Cedars Sinai Medical Center, 8700 Beverly Boulevard, B-131, Los Angeles, CA, 90048, USA

    Fnu Deepinder MD

Authors
  1. Fnu Deepinder MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fnu Deepinder MD .

Editor information

Editors and Affiliations

  1. University of Florida, Director, Robotic Surgery, Winter Haven Hospital &, 200 Avenue F. N.E., Winter Haven, 33881, Florida, USA

    Sijo J. Parekattil

  2. Center for Reproductive Medicine, Department of Urology, Cleveland Clinic, Euclid Avenue 9500, Cleveland, 44195, Ohio, USA

    Ashok Agarwal

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Deepinder, F. (2012). Novel Approaches in the Management of Klinefelter Syndrome. In: Parekattil, S., Agarwal, A. (eds) Male Infertility. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3335-4_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3335-4_19

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3334-7

  • Online ISBN: 978-1-4614-3335-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation