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Klinefelter syndrome

Reviewed July 2008

What is Klinefelter syndrome?

Klinefelter syndrome is a chromosomal condition that affects male sexual development. Males with this condition typically have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development before birth and during puberty. A shortage of testosterone during puberty can lead to breast enlargement (gynecomastia), reduced facial and body hair, and an inability to father children (infertility). Older children and adults with Klinefelter syndrome tend to be taller than other males their age. Compared with other men, adult males with Klinefelter syndrome have an increased risk of developing breast cancer and a chronic inflammatory disease called systemic lupus erythematosus. Their chance of developing these disorders is similar to that of normal adult females.

Boys with Klinefelter syndrome may have learning disabilities and difficulty with speech and language development. They tend to be quiet, sensitive, and unassertive, but personality characteristics vary among males with this condition.

Most males with Klinefelter syndrome have one extra copy of the X chromosome in each cell. Variants of Klinefelter syndrome involve more than one extra X chromosome or extra copies of both the X and Y chromosomes in each cell. These conditions tend to have more severe signs and symptoms than classic Klinefelter syndrome. In addition to affecting male sexual development, variants of Klinefelter syndrome are associated with decreased IQ, distinctive facial features, skeletal abnormalities, poor coordination, and severe problems with speech.

How common is Klinefelter syndrome?

Klinefelter syndrome affects 1 in 500 to 1,000 males. Most variants of Klinefelter syndrome are much rarer, occurring in 1 in 50,000 or fewer male births. Klinefelter syndrome does not occur in females.

What are the genetic changes related to Klinefelter syndrome?

Klinefelter syndrome is a condition related to the X chromosome and Y chromosome (the sex chromosomes). People typically have two sex chromosomes in each cell: females have two X chromosomes (46,XX), and males have one X and one Y chromosome (46,XY). Most often, Klinefelter syndrome results from the presence of a single extra copy of the X chromosome in each of a male's cells (47,XXY). Extra copies of genes on the X chromosome interfere with male sexual development, preventing the testes from functioning normally and reducing the levels of testosterone.

Some males with Klinefelter syndrome have the extra X chromosome in only some of their cells; in these individuals, the condition is described as mosaic Klinefelter syndrome (46,XY/47,XXY). Individuals with mosaic Klinefelter syndrome may have milder signs and symptoms depending on how many cells have an additional X chromosome.

Variants of Klinefelter syndrome are caused by several extra copies of the X chromosome or extra copies of both the X and Y chromosomes in all of the body's cells. The signs and symptoms of these conditions typically become more severe as the number of X chromosomes increases.

Can Klinefelter syndrome be inherited?

This condition is not inherited; it usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain one or more extra copies of the X chromosome as a result of nondisjunction. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have one or more extra X chromosomes in each of the body's cells.

Mosaic 46,XY/47,XXY is also not inherited. It occurs as a random event during cell division early in fetal development. As a result, some of the body's cells have one X chromosome and one Y chromosome (46,XY), and other cells have an extra copy of the X chromosome (47,XXY).

Where can I find information about treatment for Klinefelter syndrome?

You may find information on treatment or management of Klinefelter syndrome or some of its symptoms in the links below, particularly the links for MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about Klinefelter syndrome?

You may find the following resources about Klinefelter syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Klinefelter syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/000382.htm)
    • Encyclopedia: Testicular Failure (http://www.nlm.nih.gov/medlineplus/ency/article/000395.htm)
    • Health Topic: Klinefelter's Syndrome (http://www.nlm.nih.gov/medlineplus/klinefelterssyndrome.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/GARD/Disease.aspx?PageID=4&DiseaseID=8705)
  • Additional NIH Resources - National Institutes of Health
    • National Human Genome Research Institute (http://www.genome.gov/19519068)
    • National Institute of Child Health and Human Development: Klinefelter Syndrome (http://www.nichd.nih.gov/health/topics/klinefelter_syndrome.cfm)
    • National Institute of Child Health and Human Development: Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families (http://www.nichd.nih.gov/publications/pubs/klinefelter.cfm)
  • Educational resources - Information pages
    • Ask the Geneticist: Klinefelter syndrome and breast cancer risk (http://www.genetics.emory.edu/ask/question.php?question_id=667)
    • Ask the Geneticist: Klinefelter syndrome and fertility (http://www.genetics.emory.edu/ask/question.php?question_id=2244)
    • California Department of Developmental Services (http://www.ddhealthinfo.org/coursebuilder/?id=25)
    • Centre for Genetics Education (http://www.genetics.com.au/pdf/factsheets/fs31.pdf)
    • Genetic Science Learning Center, University of Utah (http://learn.genetics.utah.edu/content/disorders/whataregd/klinefelter/index.html)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,195/)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=484)
    • The Merck Manual Home Edition for Patients and Caregivers (http://www.merck.com/mmhe/sec23/ch266/ch266g.html)
  • Patient support - For patients and families
    • American Association for Klinefelter Syndrome Information and Support (http://www.aaksis.org/)
    • Family Village (http://www.familyvillage.wisc.edu/lib_klin.htm)
    • Intersex Society of North America (http://www.isna.org/)
    • Klinefelter Syndrome and Associates (http://www.genetic.org/knowledge/support/action/199/)
    • National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Klinefelter+Syndrome)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/chromoso.html#xxy)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Genetic Tools - Teaching cases (http://www.genetests.org/servlet/access?fcn=y&filename=/tools/cases/klinefelter-28/)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22klinefelter+syndrome%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Klinefelter+Syndrome[MAJR])+AND+(Klinefelter+syndrome[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1440+Days)

What other names do people use for Klinefelter syndrome?

  • Klinefelter's Syndrome
  • 47,XXY
  • XXY syndrome
  • XXY trisomy

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Klinefelter syndrome?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding Klinefelter syndrome?

atypical ; cancer ; cell ; cell division ; chromosome ; chronic ; egg ; gene ; gynecomastia ; hormone ; hypogonadism ; infertility ; IQ ; learning disability ; lupus ; mosaic ; nondisjunction ; puberty ; reproductive cells ; sex chromosomes ; sign ; sperm ; symptom ; syndrome ; systemic lupus ; systemic lupus erythematosus ; testes ; testosterone ; trisomy

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Bender BG, Harmon RJ, Linden MG, Bucher-Bartelson B, Robinson A. Psychosocial competence of unselected young adults with sex chromosome abnormalities. Am J Med Genet. 1999 Apr 16;88(2):200-6. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10206242)
  • Bender BG, Harmon RJ, Linden MG, Robinson A. Psychosocial adaptation of 39 adolescents with sex chromosome abnormalities. Pediatrics. 1995 Aug;96(2 Pt 1):302-8. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=7630689)
  • Bender BG, Linden MG, Harmon RJ. Neuropsychological and functional cognitive skills of 35 unselected adults with sex chromosome abnormalities. Am J Med Genet. 2001 Sep 1;102(4):309-13. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11503155)
  • Cammarata M, Di Simone P, Graziano L, Giuffre M, Corsello G, Garofalo G. Rare sex chromosome aneuploidies in humans: report of six patients with 48,XXYY, 49,XXXXY, and 48,XXXX karyotypes. Am J Med Genet. 1999 Jul 2;85(1):86-7. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10377019)
  • Graham JM Jr, Bashir AS, Stark RE, Silbert A, Walzer S. Oral and written language abilities of XXY boys: implications for anticipatory guidance. Pediatrics. 1988 Jun;81(6):795-806. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=3368277)
  • Manning MA, Hoyme HE. Diagnosis and management of the adolescent boy with Klinefelter syndrome. Adolesc Med. 2002 Jun;13(2):367-74, viii. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11986043)
  • Simpson JL, de la Cruz F, Swerdloff RS, Samango-Sprouse C, Skakkebaek NE, Graham JM Jr, Hassold T, Aylstock M, Meyer-Bahlburg HF, Willard HF, Hall JG, Salameh W, Boone K, Staessen C, Geschwind D, Giedd J, Dobs AS, Rogol A, Brinton B, Paulsen CA. Klinefelter syndrome: expanding the phenotype and identifying new research directions. Genet Med. 2003 Nov-Dec;5(6):460-8. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14614399)
  • Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA; UK Clinical Cytogenetics Group. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst. 2005 Aug 17;97(16):1204-10. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16106025)
  • Visootsak J, Aylstock M, Graham JM Jr. Klinefelter syndrome and its variants: an update and review for the primary pediatrician. Clin Pediatr (Phila). 2001 Dec;40(12):639-51. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11771918)
  • Visootsak J, Rosner B, Dykens E, Tartaglia N, Graham JM Jr. Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and 49,XXXXY. Am J Med Genet A. 2007 Jun 1;143A(11):1198-203. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17497714)
  • Wattendorf DJ, Muenke M. Klinefelter syndrome. Am Fam Physician. 2005 Dec 1;72(11):2259-62. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16342850)
  • Williams BH, Berdanier CD. Effects of diet composition and adrenalectomy on the lipogenic responses of rats to starvation-refeeding. J Nutr. 1982 Mar;112(3):534-41. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=7062147)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2008
Published: May 4, 2009