Johns Hopkins Division of Infectious Diseases
M E N S  H E A L T H  G U I D E
search:



Men's Health Sponsors About this site Site Map
Expert Questions & AnswersFeature Articles
HOME DISEASES
  Kleinfelter's syndrome
 
Authors: Shehzad Basaria, MD, Adrian Dobs Last modified: January 3, 2002
DIAGNOSTIC CRITERIA

  EPIDEMIOLOGY

  • Described by Harry Klinefelter in 1942. In 1959 found to be related to a 47, XXY chromosomal abnormality
  • Estimates of 1:500-1000 male births, making it the most common congenital abnormality causing primary hypogonadism.
  • Although the most common presentation is delayed puberty during the teen years, a few patients are diagnosed at a later age when they present with infertility.

  RISK FACTORS

  • Chromosomal constitution due to nondisjunction of the sex chromosomes of either parent during first or second meiotic division.
  • Although the most common genotype is 47,XXY, greater or lesser number of chromosomes have also been reported.
  • Mosaicism (46,XY/46,XXY) is also seen. Mosaicism occurs as a result of nondisjunction during mitotic division after conception.
  • The greater the number of X chromosomes, the greater the degree of phenotypic abnormalities.

  SIGNS AND SYMPTOMS

  • Pre-pubertal males may have lower birth weight, height percentiles increase with age. These males may have learning disabilities.
  • There is disproportionate increase in leg length.
  • Post-pubertal male phenotype includes small firm testes, decreased facial and body hair, and low pitched voice.
  • The majority of men are azoospermic due to hyalinization of testes. Gynaecomastia is also common due to altered testosterone/estrogen ratio.
  • The incidence of autoimmune endocrine disorders is slightly increased, e.g. 10% of men have antibodies to thyroglobulin, 19% with impaired glucose tolerance.
  • There is an increase in the incidence of germ cell tumors of the mediastinum.
  • Breast cancer - increased risk related to breast size. Men complaining of mastalgia should undergo mammogram.
  • There is an increase in the incidence of pulmonary diseases (bronchiectasis, emphysema) and varicose veins (venous ulcers).
  • General symptoms of hypogonadism - erectile dysfunction, decreased libido, decreased energy and muscle mass, ostopenia, ostoeporosis

  DIFFERENTIAL DIAGNOSIS

  • Delayed puberty
  • Kallman's syndrome - Hypogonadotrophic hypogonadism
  • Hypopituitarism
  • Infections of the testes (mumps orchitis)
  • Radiation damage to the testes.

  LABORATORY FINDINGS

  • Elevated FSH and LH, usually in the presence of a low or borderline low serum testosterone
  • XXY karyotype
  • Osteopenia or osteoporosis on DEXA scan
 
TREATMENT
TESOSTERONE REPLACEMENT THERAPY
  • Testoderm TTS (Transdermal Testosterone System) 5-10 mg/day.
  • Androgel 5-10 gm/day.
  • Since paternity has been reported in a few of these patients, testicular biopsy and cryopreservation of sperms for IVF is an option in those who desire children.
CALCIUM 1500 MG, VITAMIN D 400 UNITS MAY BE INDICATED FOR BONE DENSITY
 
IMPORTANT POINTS/RECOMMENDATIONS
  • Treatment with testosterone should begin at the time of usualy puberty in boys. Pre-pubertal treatment is still controversial and generally not recommened at this point.
  • Men with serum testosterone levels within the normal range, but with elevated gonadotropins still should be treated, especially in the face of decreased bone density
 
REFERENCES
  1. Klinefelter HF ;  Syndrome characterized by gynecoastia, aspermatogenesis without a Leydigism and ncrased excreation of follcile -stimulating hormone ;  J Clin Endocrinol Metab 1942;2:615-627

  2. Jacobs PA, Strong JA ;  A case of human intersexuality having a possible XXY sex-determining mechanism ;  Nature 1959;83:302-3

  3. Hasle H, Mellemgaard A, Nielsen J ;  Cancer incidence in men with Klinefelter syndrom ;  Br J Cancer 1995;71:416-20

  4. Wang C, Baler HWG, Burger HG. ;  Hormonal studies in Klinefelter's syndrome. ;  Clin Endocrinol 1975;4:399.

Copyright © 2002 The Johns Hopkins University School of Medicine. All rights reserved.