Klinefelter Syndrome

Klinefelter Syndrome

National Organization for Rare Disorders, Inc.

Important

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.

Synonyms

  • KS
  • XXY male
  • XX male
  • XXYY male
  • XXXY male
  • XXXXY male

Disorder Subdivisions

  • None

General Discussion

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 variant forms of Klinefelter syndrome 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.

Symptoms

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 higher than average frequency of delayed development of language skills. 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.

Causes

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.

Affected Populations

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. Variant forms of the condition occur much less frequently.

Standard Therapies

Diagnosis

Klinefelter syndrome is diagnosed by a chromosome analysis on a blood sample. This condition can also be diagnosed prenatally on chorionic villous or amniotic fluid cells.



Treatment

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 at the age of approximately 11 or 12 years of age. 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.



Men with Klinefelter syndrome were once considered 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.

Investigational Therapies

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:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOK

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.



JOURNAL ARTICLES

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.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



49 XXXXY

870 Miranda Green

Palo Alto, CA 94306

USA

Tel: (360)892-7547

Email: epwatzka@gmail.com

Internet: http://www.xxxxysyndrome.com/index.htm



Klinefelter Syndrome Association of Canada

42 Ritson Road South, Upper floor,

Oshawa

Ontario, L1H 5G9

Canada

Tel: 9059262942

Email: dj.rabinovitch@gmail.com



NIH/National Institute of Child Health and Human Development

31 Center Dr

Building 31, Room 2A32

MSC2425

Bethesda, MD 20892

Fax: (866)760-5947

Tel: (800)370-2943

TDD: (888)320-6942

Email: NICHDInformationResourceCenter@mail.nih.gov

Internet: http://www.nichd.nih.gov/



American Association for Klinefelter Syndrome Information and Support

c/o Roberta Rappaport

2945 W. Farwell Avenue

Chicago, IL 60645-2925

USA

Tel: (773)761-5298

Fax: (773)761-5298

Tel: (888)466-5747

Email: KSinfo@aaksis.org

Internet: http://www.aaksis.org



Klinefelters Syndrome Support Group of Australia

Kellyville

New South Wales, 2155

Australia

Tel: 04 25240773

Email: YATESBECKS@bigpond.com



XXYY Project

PO Box 2172

Littleton, CO 80161-2172

USA

Tel: (215)394-5942

Email: inquiry@xxyysyndrome.org

Internet: http://xxyysyndrome.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Klinefelter Syndrome & Associates

P.O. Box 872

Pine, CO 80470-0872

Tel: (303)400-9040

Fax: (303)838-0753

Tel: (888)999-9428

Email: info@genetic.org

Internet: http://www.genetic.org



Focus Foundation, Inc.

PO Box 190

Davidsonville, MD 21035

Tel: (443)223-7323

Fax: (410)798-4801

Email: info@thefocusfoundation.org

Internet: http://www.thefocusfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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