National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Klinefelter Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
Related Disorders List
Information on the following diseases can be found in the Related Disorders section of this report:
Klinefelter syndrome is a group of chromosomal disorders in males in which one or more extra X chromosomes are present. Males with the classic form of the disorder have one extra X chromosome. Males with other X and Y variations have additional X and/or Y chromosomes. The extra X and/or Y chromosome can affect physical, developmental, behavioral, and cognitive functioning. Common physical features may include tall stature, lack of secondary pubertal development, small testes (hypogonadism), delayed pubertal development, and breast development (gynecomastia) in late puberty. These features may be associated with low testosterone level and elevated gonadotropin levels.
Infants and young children with Klinefelter syndrome are sometimes initially identified because of an abnormality in the location of the urinary opening in the penis (hypospadias), small penis or testes, or developmental delay (e.g. speech delay). Older children and teenagers are sometimes diagnosed with Klinefelter syndrome if secondary sexual characteristics do not develop completely, puberty is delayed, testes are small or breast development occurs. Many males with Klinefelter syndrome are not identified until they have infertility problems as adults. Men with Klinefelter syndrome may have a relatively increased risk to develop breast cancer. Most males with Klinefelter syndrome have normal intelligence but there is a high risk of language delay and social functioning challenges. There is a correlation between the number of extra X chromosomes and the degree of physical and intellectual deficits.
Men with Klinefelter syndrome may have an increased risk for endocrine conditions such as diabetes mellitus, hypothyroidism and hypoparathyroidism and autoimmune diseases such as systemic lupus erythematosus, Sjogren syndrome and rheumatoid arthritis. For more information about these conditions, please search for them in by name in NORD's Rare Disease Database.
Males with Klinefelter syndrome have one or more extra X chromosomes because of an error that occurs during the division of the sex chromosomes in the egg or sperm. Some males with Klinefelter syndrome are mosaic, meaning that some cells have an extra X chromosome and other cells do not. Mosaic Klinefelter syndrome occurs because of an error in the division of the sex chromosomes in the zygote after fertilization.
The extra X chromosome results in primary testicular failure leading to androgen deficiency.
The classic form of Klinefelter syndrome in which one extra X chromosome is present in all cells, occurs in approximately 1 in 500-1000 males. 80-90% of affected males have the classic type. Other X and Y variant forms of the condition occur much less frequently.
Kallmann syndrome is a rare inherited disorder that mostly, but not exclusively, affects men. The major characteristics of Kallmann syndrome, in both men and women, are the failure to experience puberty and the complete or partial loss of the sense of smell. Failure to go through puberty reflects a hormonal imbalance that is caused by a failure of a part of the brain known as the hypothalamus. Patients with Kallmann syndrome show evidence of small genitalia, sterile gonads that cannot produce the sex cells (hypogonadism), and a loss of the sense of smell (anosmia). The impaired production of hormones as well as sperm and egg cells causes delayed puberty, growth and infertility. (For more information on this disorder, choose "Kallmann syndrome" as your search term in the Rare Disease Database.)
Klinefelter syndrome is diagnosed by a chromosome karyotype analysis on a blood sample. This condition can also be diagnosed prenatally on chorionic villous or amniotic fluid cells.
Klinefelter syndrome is treated with the administration of male hormones (androgens), such as testosterone enanthate or cypionate. These are given to promote the development of secondary male sexual characteristics (virilization). This hormone therapy should begin around pubertal development. Some men with Klinefelter syndrome who have gynecomastia may require surgical breast reduction for cosmetic purposes.
Speech and language therapy, physical therapy and occupational therapy may be helpful for boys with Klinefelter syndrome. A comprehensive psychoeducational evaluation is recommended to determine what resources may be helpful in the classroom. Social skills training classes can also be beneficial.
Men with Klinefelter syndrome tend to be infertile but a few men with mosaic Klinefelter syndrome have been reported to be fertile. Surgical extraction of sperm from the testes and intracytoplasmic sperm injection (ICSI) directly into an ovum is a medical technology available to assist some men with Klinefelter syndrome to father children.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
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De la Chapelle A. Sex Chromosome Abnormalities. In: Emery AEH, Rimoin DL, eds. Principles and Practice of Medical Genetics. Vol 1. Edinburgh, England: Churchill Livingstone; 1990:273-299.
Samango-Sprouse CA, Gropman AL, Sadeghin T, et al. Effects of short-course androgen therapy on the neurodevelopmental profile of infants and children with 49,XXXXY syndrome. Acta Paediatr. 2011;100(6):861-5.
Samango-Sprouse CA. Expansion of the phenotypic profile of the young child with XXY. Pediatr Endocrinol Rev. 2010;8 Suppl 1:160-8.
Visootsak J, Graham JM Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare Dis. 2006;1:42.
Wikstrom AM, Painter JN, Raivio T, Aittomaki K, Dunkel L. Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome. Clin Endocrinol (Oxf). 2006;65(1):92-7.
Schiff JD, Palermo GD, Veeck LL, et al. Success of testicular sperm injection and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab. 2005;90(11):6263-7.
Swerdlow AJ, Higgins CD, Schoemaker MJ, et al. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. J Clin Endocrinol Metab. 2005;90(12):6516-22.
Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA,. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst. 2005;97(16):1204-10.
Wattendorf DJ, Muenke M. Klinefelter syndrome. Am Fam Physician. 2005;72(11):2259-62.
Denschlag D, Tempfer C, Kunze M, Wolff G, Keck C. Assisted reproductive techniques in patients with Klinefelter syndrome: a critical review. Fertil Steril. 2004;82(4):775-9.
Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003;88(2):622-6.
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.
Linden MG, Bender BG, Robinson A. Sex chromosome tetrasomy and pentasomy. Pediatrics. 1995;96(4 Pt 1):672-82.
Kleczkowska A, Fryns JP, Van den Berghe H. X-chromosome polysomy in the male. The Leuven experience 1966-1987. Hum Genet. 1988;80(1):16-22.
March of Dimes Birth Defects Foundation
1275 Mamaroneck Avenue
White Plains, NY 10605
870 Miranda Green
Palo Alto, CA 94306
Klinefelter Syndrome Association of Canada
42 Ritson Road South, Upper floor,
Ontario, L1H 5G9
NIH/National Institute of Child Health and Human Development
31 Center Dr
Building 31, Room 2A32
Bethesda, MD 20892
American Association for Klinefelter Syndrome Information and Support
c/o Roberta Rappaport
3796 Ogden Ln.
Mundelein, IL 60060-6038
Klinefelters Syndrome Support Group of Australia
New South Wales, 2155
Tel: 04 25240773
PO Box 2172
Littleton, CO 80161-2172
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
Klinefelter Syndrome & Associates
P.O. Box 872
Pine, CO 80470-0872
Focus Foundation, Inc.
PO Box 190
Davidsonville, MD 21035
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It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report
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Last Updated: 1/27/2014
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