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Klinefelter's syndrome

Klinefelter's syndrome
Classification & external resources
ICD-10 Q98.0-Q98.4
ICD-9 758.7
DiseasesDB 7189
eMedicine ped/1252 
MeSH D007713
Not to be confused with XYY syndrome. For the Lucía Puenzo film, see XXY (film).

Klinefelter's syndrome, 47, XXY or XXY syndrome is a condition caused by a chromosome aneuploidy. Affected males have an extra X sex chromosome. The principal effects are development of small testes and reduced fertility. A variety of other physical and behavioral differences and problems are common, though severity varies and many boys and men with the condition have few detectable symptoms. The second most common extra chromosome condition, it is named after Dr. Harry Klinefelter, an endocrinologist at Massachusetts General Hospital, Boston, Massachusetts, who first described it in 1942.[1] The condition exists in roughly 1 out of every 500 to 1,000 males.[2] Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47,XXY Males".[3]


Signs and symptoms

Affected males are almost always effectively sterile, although advanced reproductive assistance is sometimes possible.[4] Some degree of language learning impairment may be present.[5] In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue).[6] Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher percentage than in the XY population, but only about 10% of XXY males' gynecomastia is noticeable enough to require surgery.[7]

The term "hypogonadism" in XXY symptoms is often misinterpreted to mean "small testicles" or "small penis". In fact, it means decreased testicular hormone/endocrine function. Because of this hypogonadism, patients will often have a low serum testosterone level but high serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels.[8] Despite this misunderstanding of the term, however, it is true that XXY men often also have "microorchidism" (i.e. small testicles).[8]

The more severe end of the spectrum of symptom expression is also associated with an increased risk of germ cell tumors,[9] breast cancer,[10] and osteoporosis,[2] risks shared to varying degrees[11] with females. Additionally, extant medical literature shows some individual case studies of Klinefelter's syndrome coexisting with other disorders, such as pulmonary disease, varicose veins, diabetes mellitus, and rheumatoid arthritis, but the etiologies (understanding of any potential causation relationship) between Klinefelter's and these other conditions are not well characterized or understood.

In contrast to these potentially increased risks, it is currently thought that rare X-linked recessive conditions occur even less frequently in XXY males than in normal XY males, since these conditions are transmitted by genes on the X chromosome, and people with three X chromosomes are typically only carriers rather than affected by these X-linked recessive conditions.

There are many variances within the XXY population, just as in the most common 46,XY population. While it is possible to characterise 47,XXY males with certain body types, that in itself should not be the method of identification as to whether or not someone has 47,XXY. The only reliable method of identification is karyotype testing.


The extra X chromosome is retained because of a nondisjunction event during meiosis (sex cell division). The XXY chromosome arrangement is one of the most common genetic variations from the XY karyotype, occurring in about 1 in 500 to 1,000 live male births.[2]

In mammals with more than one X chromosome, the genes on all but one X chromosome are not expressed; this is known as X inactivation. This happens in XXY males as well as normal XX females.[12] A few genes located in the pseudoautosomal regions, however, have corresponding genes on the Y chromosome and are capable of being expressed.[13] These triploid genes in XXY males may be responsible for symptoms associated with Klinefelter's syndrome.[citation needed]

The first published report of a man with a 47,XXY karyotype was by Patricia A. Jacobs and Dr. J.A. Strong at Western General Hospital in Edinburgh, Scotland in 1959.[14] This karyotype was found in a 24-year-old man who had signs of Klinefelter's syndrome. Dr. Jacobs described her discovery of this first reported human or mammalian chromosome aneuploidy in her 1981 William Allan Memorial Award address.[15]


The genetic variation is irreversible, but its symptoms can be altered or treated in a number of ways, including the use of testosterone treatment.[citation needed]

Inadequately treated hypogonadism in Klinefelter syndrome increases recognized psychosocial morbidity]].[16] At least one study indicates that planned and timed support should be provided for young men with Klinefelter syndrome, to ameliorate current poor psychosocial outcomes.[16]

Kathleen o'keefe is a common example of this rare disorder


The 48, XXYY (male) syndrome occurs 1 in 17,000 births and has traditionally been considered to be a variation of Klinefelter's syndrome. XXYY is no longer generally considered a variation of KS, although it has not yet been assigned an ICD-10 code.

Males with Klinefelter syndrome may have a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome is very rare. Thus far, only about 10 cases have been described in literature.[17]


Patients with Klinefelter syndrome have a 50 times greater risk of germ cell tumors (GSTs).[9] In these patients, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are testicular in location.


  1. ^ Klinefelter, HF Jr; Reifenstein, EC Jr & Albright (1942), " ", J Clin Endocrinol Metab 2: 615-624, PMID: too early to be indexed. Klinefelter, HF (1986), " ", South Med J 79 (9): 1089-1093, PMID: 3529433 talks about the history of the development of the literature.
  2. ^ a b c Klinefelter Syndrome (HTML). Health Information. National Institute of Health and Human Development (2007-02-19). Retrieved on 2007-03-24. and Klinefelter syndrome (HTML). Genetics Home Reference. National Library of Medicine (2006). Retrieved on 2007-03-24. both provide statistical estimates.
  3. ^ Bock, Robert (1993 Aug). Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families (HTML). NIH Pub. No. 93-3202. Office of Research Reporting, NICHD. Retrieved on 2007-04-07.
  4. ^ Denschlag, Dominik, MD; Clemens, Tempfer, MD & Kunze, Myriam, MD et al. (October 2004), " ", Fertility and Sterility 82 (4): 775-779, DOI 10.1016/j.fertnstert.2003.09.085
  5. ^ Graham, JM Jr; Bashir, AS & Stark, RE et al. (June 1988), " ", Pediatrics 81 (6): 795-806, PMID: 3368277
  6. ^ Abstract of Klinefelter, HF (1986), " ", South Med J 79 (9): 1089-1093, PMID: 3529433 provides information on microorchidism (small testes), hypogonadism (infertility/sterility and androgen hormone function) and gynecomastia. Bock, Robert (1993 Aug). Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families (HTML). NIH Pub. No. 93-3202. Office of Research Reporting, NICHD. Retrieved on 2007-03-28. offers substantive information about body type and appearance until a more rigorous source is found/supplied.
  7. ^ Bock, Robert (1993 Aug). Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families, Adolescence section (HTML). NIH Pub. No. 93-3202. Office of Research Reporting, NICHD. Retrieved on 2007-03-29. describes statistical occurrence of gynecomastia and surgical treatment.
  8. ^ a b Leask, Kathryn (October 2005). Klinefelter syndrome (HTML). National Library for Health, Specialist Libraries, Clinical Genetics. National Library for Health. Retrieved on 2007-04-07.
  9. ^ a b Gregory G. Bebb, Frederic W. Grannis, Jr, Isaac B. Paz, Marilyn L. Slovak, Robert Chilcote (1998). Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome. Annals of Thoracic Surgery 66: 547-548. Retrieved on December 25, 2007.
  10. ^ Hultborn, R; Hanson, C & Kopf, I et al. (1997 Nov-Dec), " ", Anticancer Res. 17 (6D): 4293-4297, PMID: 9494523
  11. ^ For instance, while Hultborn, R; Hanson, C & Kopf, I et al. (1997 Nov-Dec), " ", Anticancer Res. 17 (6D): 4293-4297, PMID: 9494523 shows a 50-fold increased risk of developing breast cancer versus normal males, study of the SEER Cancer Statistics Review (CSR) databases available at the National Cancer Institute reveal that female relative risk of breast cancer incidence compared to normal males is around a 100 to 200-fold increase, which indicates XXY males may not be as much at risk statistically as normal females are.
  12. ^ Chow J, Yen Z, Ziesche S, Brown C (2005). "Silencing of the mammalian X chromosome". Annu Rev Genomics Hum Genet 6: 69-92. PMID 16124854
  13. ^ Blaschke RJ, Rappold G (2006). The pseudoautosomal regions, SHOX and disease. Curr Opin Genet Dev. Jun; 16:233-9. PMID 16650979
  14. ^ Jacobs PA, Strong JA (January 31, 1959). "A case of human intersexuality having a possible XXY sex-determining mechanism". Nature 183 (4657): 302-3. PMID 13632697.
  15. ^ Jacobs PA (September 1982). "The William Allan Memorial Award address: human population cytogenetics: the first twenty-five years". Am J Hum Genet 34 (5): 689-98. PMID 6751075.
  16. ^ a b Simm PJ, Zacharin MR. "The psychosocial impact of Klinefelter syndrome--a 10 year review". J Pediatr Endocrinol Metab 2006 Apr;19(4):499-505. PMID 16759035
  17. ^ Velissariou V, Christopoulou S, Karadimas C, Pihos I, Kanaka-Gantenbein C, Kapranos N, Kallipolitis G, Hatzaki A. (July - August 2006). "Rare XXY/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report". Eur J Med Genet 49 (4): 331-337. PMID 16829354

See also

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Klinefelter's_syndrome". A list of authors is available in Wikipedia.
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