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| {{Infobox_Disease | | | {{Infobox_Disease | |
| Name = {{PAGENAME}} | | | Name = {{PAGENAME}} | |
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| eMedicineSubj = ped |
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| eMedicineTopic = 1252 |
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| MeshID = D007713 | | | MeshID = D007713 | |
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| {{SI}} | | {{Klinefelter's syndrome}} |
| | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
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| :''Not to be confused with [[XYY syndrome]] or [[XXX syndrome]].'' | | :''Not to be confused with [[XYY syndrome]] or [[XXX syndrome]].'' |
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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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| {{CMG}} | | {{CMG}} |
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| {{Editor Help}} | | {{SK}} 47XXY; XXY syndrome; XXY male. |
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| ==Overview== | | ==[[Klinefelter's syndrome overview|Overview]]== |
| '''Klinefelter's syndrome''', '''47,XXY''' or '''XXY syndrome''' is a condition caused by a [[chromosome]] [[aneuploidy]]. Affected males have an extra [[XY sex-determination system|X sex chromosome]]. The principal effects are development of small [[testicles]] 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.<ref name="kline1942">{{Citation| last = Klinefelter | first = HF Jr | last2 = Reifenstein | first2 = EC Jr | last3 = Albright | title = Syndrome characterized by gynecomastia, aspermatogenesis without a-Leydigism and increased excretion of follicle-stimulating hormone. | journal = J Clin Endocrinol Metab | volume = 2 | pages = 615–624 | date = 1942 | year = 1942 | pmid = ''too early to be indexed''}}. {{Citation| last = Klinefelter | first = HF | title = Klinefelter's syndrome: historical background and development. | journal = South Med J | volume = 79 | issue = 45| pages = 1089–1093 | date = 1986 | year =1986 | pmid = 3529433}} talks about the history of the development of the literature.</ref> The condition exists in roughly 1 out of every 500 males.<ref name="nihhd2007">{{cite web| title = Klinefelter Syndrome | work = Health Information | publisher = National Institute of Health and Human Development | date = [[2007-02-19]] | url = http://www.nichd.nih.gov/health/topics/klinefelter_syndrome.cfm | format = HTML | accessdate = 2007-03-24 }} and {{cite web | title = Klinefelter syndrome | work = Genetics Home Reference | publisher = National Library of Medicine | year = 2006 | url = http://ghr.nlm.nih.gov/condition%3Dklinefeltersyndrome | format = HTML | accessdate = 2007-03-24 }} both provide statistical estimates.</ref> Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47, XXY Males".<ref name="orrnichhd1993full">{{cite web |url=http://www.nichd.nih.gov/publications/pubs/klinefelter.cfm |title=Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families |last=Bock |first=Robert |accessdate=2007-04-07 |date = 1993 Aug |year = 1993 | month = August |format=HTML |work=NIH Pub. No. 93-3202|publisher=Office of Research Reporting, NICHD}}</ref>
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| ==Signs and symptoms== | | ==[[Klinefelter's syndrome historical perspective|Historical Perspective]]== |
| Affected males are almost always effectively [[infertility|sterile]], although advanced reproductive assistance is sometimes possible.<ref name="fertstert2004">{{Citation|last = Denschlag|first = Dominik, MD|last2 = Clemens|first2 = Tempfer, MD|last3 = Kunze|first3 = Myriam, MD|last4 = Wolff|first4 = Gerhard, MD|last5 = Keck|first5 = Christoph, MD|title = Assisted reproductive techniques in patients with Klinefelter syndrome: A critical review|journal = Fertility and Sterility|volume = 82|issue = 4|pages = 775–779|date = October 2004|year = 2004|doi = 10.1016/j.fertnstert.2003.09.085}}</ref> Some degree of language learning impairment may be present,<ref name="ped1988">{{Citation|last = Graham |first = JM Jr|last2 = Bashir |first2 = AS|last3 = Stark |first3 = RE|last4 = Silbert |first4 = A|last5 = Walzer |first5 = S|title = Oral and written language abilities of XXY boys: implications for anticipatory guidance.|journal = Pediatrics|volume = 81|issue = 6|pages = 795–806|date = June 1988|year = 1988|pmid = 3368277 }}</ref> and neuropsychological testing often reveals deficits in [[executive functions]]<ref>Boone et al: (2001), "Neuropsychological profiles of adults with Klinefelter syndrome" in Journal of International Neuropsychological Society, #7, p 446-456.</ref>. 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).<ref name="smedj1986">Abstract of {{Citation|last = Klinefelter |first = HF |title = Klinefelter's syndrome: historical background and development.|journal = South Med J |volume = 79 |issue = 9|pages = 1089–1093 |date = 1986 |year = 1986 |pmid = 3529433}} provides information on microorchidism (small testes), hypogonadism (infertility/sterility and androgen hormone function) and gynecomastia. {{cite web |url=http://www.nichd.nih.gov/publications/pubs/klinefelter.cfm |title=Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families |last=Bock |first=Robert |accessdate=2007-03-28 |date = 1993 Aug |year = 1993 | month = August |format=HTML |work=NIH Pub. No. 93-3202|publisher=Office of Research Reporting, NICHD}} offers substantive information about body type and appearance until a more rigorous source is found/supplied.</ref> 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.<ref name="orr-nichd1993">{{cite web |url=http://www.nichd.nih.gov/publications/pubs/klinefelter.cfm#xadol|title=Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families, Adolescence section |last=Bock |first=Robert |accessdate=2007-03-29 |date = 1993 Aug |year = 1993 | month = August |format=HTML |work=NIH Pub. No. 93-3202|publisher=Office of Research Reporting, NICHD}} describes statistical occurrence of gynecomastia and surgical treatment.</ref>
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| 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.<ref name="nlhclingen2005">{{cite web| last = Leask | first = Kathryn | title = Klinefelter syndrome | work = National Library for Health, Specialist Libraries, Clinical Genetics | publisher = National Library for Health | date = October 2005 | url = http://www.library.nhs.uk/genepool/ViewResource.aspx?resID=104897 | format = HTML | accessdate = 2007-04-07 }}</ref> Despite this misunderstanding of the term, however, it is true that XXY men often also have "microorchidism" (i.e. small testicles).<ref name="nlhclingen2005" />
| | ==[[Klinefelter's syndrome pathophysiology|Pathophysiology]]== |
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| The more severe end of the [[spectrum]] of symptom expression is also associated with an increased risk of [[germ cell tumors]], [[breast cancer]],<ref name="anticancerres1997">{{Citation|last = Hultborn |first = R|last2 = Hanson |first2 = C|last3 = Kopf |first3 = I|last4 = Verbiene |first4 = I|last5 = Warnhammar |first5 = E|last6 = Weimarck |first6 = A |title = Prevalence of Klinefelter's syndrome in male breast cancer patients. |journal = Anticancer Res.|volume = 17 |issue = 6D |pages = 4293–4297 |date = 1997 Nov-Dec |year = 1997|pmid = 9494523}}</ref> and [[osteoporosis]],<ref name="nihhd2007" /> risks shared to varying degrees<ref name="nci2003">For instance, while {{Citation|last = Hultborn |first = R|last2 = Hanson |first2 = C|last3 = Kopf |first3 = I|last4 = Verbiene |first4 = I|last5 = Warnhammar |first5 = E|last6 = Weimarck |first6 = A |title = Prevalence of Klinefelter's syndrome in male breast cancer patients. |journal = Anticancer Res.|volume = 17 |issue = 6D |pages = 4293–4297 |date = 1997 Nov-Dec |year = 1997|pmid = 9494523}} shows a 50-fold increased risk of developing breast cancer versus normal males, study of the [http://seer.cancer.gov/csr/1975_2003/ SEER Cancer Statistics Review (CSR)] databases available at the [http://www.cancer.gov/ 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.</ref> with females. Additionally, medical literature shows some individual case studies of Klinefelter's syndrome coexisting with other disorders, such as [[pulmonary disease]], [[varicose vein]]s, [[diabetes mellitus]], and [[rheumatoid arthritis]], but possible correlations between Klinefelter's and these other conditions are not well characterized or understood.
| | ==[[Klinefelter's syndrome causes|Causes]]== |
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| In contrast to these potentially increased risks, it is currently thought that rare [[Sex linked|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 two X chromosomes are typically only carriers rather than affected by these X-linked recessive conditions.
| | == [[Differentiating Klinefelter's Syndrome from other Diseases]] == |
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| 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.
| | ==[[Klinefelter's syndrome epidemiology and demographics|Epidemiology and Demographics]]== |
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| == Diagnosis== | | ==[[Klinefelter's syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| A [[karyotype]] is used to confirm the diagnosis. In this procedure, a small blood sample is drawn. [[White blood cell]]s are then separated from the sample, mixed with [[Growth medium|tissue culture medium]], incubated, and checked for chromosomal abnormalities, such as an extra X chromosome.
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| ==Cause== | | ==Diagnosis== |
| The extra X chromosome is retained because of a [[Meiosis#Nondisjunction|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 live male births.<ref name="nihhd2007" />
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| In [[mammal]]s with more than one X chromosome, the [[gene]]s 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.<ref name="arghg2005">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</ref> A few genes located in the [[pseudoautosomal region]]s, however, have corresponding genes on the Y chromosome and are capable of being expressed.<ref name="cogd2006">Blaschke RJ, Rappold G (2006). The pseudoautosomal regions, SHOX and disease. ''Curr Opin Genet Dev''. Jun; '''16''':233-9. PMID 16650979</ref> These [[triploid]] genes in XXY males may be responsible for symptoms associated with Klinefelter's syndrome.
| | [[Klinefelter's syndrome history and symptoms|History and Symptoms]] | [[Klinefelter's syndrome physical examination|Physical Examination]] | [[Klinefelter's syndrome laboratory findings|Laboratory Findings]] |
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| 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.<ref name="nature1959">{{cite journal |author=Jacobs PA, Strong JA |month=January 31, |year=1959 |title=A case of human intersexuality having a possible XXY sex-determining mechanism |journal=[[Nature (journal)|Nature]] |volume=183 |issue=4657 |pages=302–3 |pmid=13632697 |doi= 10.1038/183302a0}}</ref> 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.<ref name="amjhumgenet1982">{{cite journal |author=Jacobs PA |month=September |year=1982 |title=The William Allan Memorial Award address: human population cytogenetics: the first twenty-five years |journal=[[American Journal of Human Genetics|Am J Hum Genet]] |volume=34 |issue=5 |pages=689–98 |pmid=6751075 |url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1685430&blobtype=pdf}}</ref>
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| ==Treatment== | | ==Treatment== |
| The genetic variation is irreversible, but its symptoms can be altered or treated in a number of ways, including testosterone treatment and other therapies.
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| Inadequately treated [[hypogonadism]] in Klinefelter syndrome increases recognized psychosocial morbidity.<ref name="jpediatrendo2006">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</ref> 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.<ref name="jpediatrendo2006" />
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| ==Variations==
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| 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-9 code.
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| Males with Klinefelter syndrome may have a [[Mosaic (genetics)|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.<ref name="eurjmedgenet2006">Velissariou V, Christopoulou S, Karadimas C, Pihos I, Kanaka-Gantenbein C, Kapranos N, Kallipolitis G, Hatzaki A. "Rare XXY/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report". '' Eur J Med Genet'' 2006 July - August;49(4):331-337. PMID 16829354</ref>
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| ==Complications==
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| Patients with Klinefelter syndrome have a 50 times greater risk of [[germ cell tumors]] (GSTs).<ref>Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome. Gregory G. Bebb, Frederic W. Grannis, Jr, Isaac B. Paz, Marilyn L. Slovak, Robert Chilcote. Ann Thorac Surg 1998;66:547-548. [http://ats.ctsnetjournals.org/cgi/content/abstract/66/2/547 Online}</ref> In these patients, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are testicular in location.
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| ==References==
| | [[Klinefelter's syndrome medical therapy|Medical Therapy]] | [[Klinefelter's syndrome surgery|Surgery]] |
| {{Reflist|2}}
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| == See also == | | == Related Chapters == |
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| * [[Intersexuality]] | | * [[Intersexuality]] |
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| * [[XYY syndrome]] | | * [[XYY syndrome]] |
| * [[True hermaphroditism]] | | * [[True hermaphroditism]] |
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| == External links ==
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| * [http://www.bidmc.org/YourHealth/ConditionsAZ.aspx?ChunkID=11722 Beth Israel Deaconess Medical Center: Klinefelter's syndrome]
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| * {{DMOZ|Health/Conditions_and_Diseases/Genetic_Disorders/Klinefelter_Syndrome/}}
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| {{Chromosomal abnormalities}} | | {{Chromosomal abnormalities}} |
| {{SIB}}
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| [[Category:Genetic disorders]]
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| [[Category:Syndromes]]
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| [[Category:Intersexuality]]
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| [[cs:Klinefelterův syndrom]] | | [[cs:Klinefelterův syndrom]] |
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