GTS5:Klinefelter syndrome: Difference between revisions
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==Definition/Description of Disease== | ==Definition/Description of Disease== | ||
Klinefelter syndrome (KS) is a genetic condition affecting males and results from the presence of an extra X chromosome (47,XXY). KS can lead to a range of physical, developmental and reproductive issues, including tall stature, reduced muscle mass, gynecomastia, small testes, infertility, azoospermia and learning difficulties.<ref>{{Cite journal|last=Bearelly|first=Priyanka|last2=Oates|first2=Robert|date=2019|title=Recent advances in managing and understanding Klinefelter syndrome|url=https://pubmed.ncbi.nlm.nih.gov/30755791|journal=F1000Research|volume=8|pages=F1000 Faculty Rev–112|doi=10.12688/f1000research.16747.1|issn=2046-1402|pmc=6352920|pmid=30755791}}</ref> There is a high incidence of symptom variability, and many individuals remain undiagnosed. KS should be suspected in adolescence in males with incomplete or delayed puberty, eunuchoid body habitus (disproportionately long arms and legs), gynecomastia, small and firm testes, low muscle mass, and psychosocial difficulties, and in adults with primary hypogonadism (small testes low testosterone, high FSH/LH), azoospermia, reduced libido or erectile dysfunction, osteoporosis, and mild cognitive or language difficulties.<ref>{{Cite journal|last=Bojesen|first=Anders|last2=Gravholt|first2=Claus H.|date=2007-04|title=Klinefelter syndrome in clinical practice|url=https://pubmed.ncbi.nlm.nih.gov/17415352|journal=Nature Clinical Practice. Urology|volume=4|issue=4|pages=192–204|doi=10.1038/ncpuro0775|issn=1743-4289|pmid=17415352}}</ref><ref name=":0">{{Cite journal|last=Groth|first=Kristian A.|last2=Skakkebæk|first2=Anne|last3=Høst|first3=Christian|last4=Gravholt|first4=Claus Højbjerg|last5=Bojesen|first5=Anders|date=2013-01|title=Clinical review: Klinefelter syndrome--a clinical update|url=https://pubmed.ncbi.nlm.nih.gov/23118429|journal=The Journal of Clinical Endocrinology and Metabolism|volume=98|issue=1|pages=20–30|doi=10.1210/jc.2012-2382|issn=1945-7197|pmid=23118429}}</ref> | Klinefelter syndrome (KS) is a genetic condition affecting males and results from the presence of an extra X chromosome (47,XXY). KS can lead to a range of physical, developmental and reproductive issues, including tall stature, reduced muscle mass, gynecomastia, small testes, infertility, azoospermia and learning difficulties.<ref>{{Cite journal|last=Bearelly|first=Priyanka|last2=Oates|first2=Robert|date=2019|title=Recent advances in managing and understanding Klinefelter syndrome|url=https://pubmed.ncbi.nlm.nih.gov/30755791|journal=F1000Research|volume=8|pages=F1000 Faculty Rev–112|doi=10.12688/f1000research.16747.1|issn=2046-1402|pmc=6352920|pmid=30755791}}</ref> There is a high incidence of symptom variability, and many individuals remain undiagnosed. KS should be suspected in adolescence in males with incomplete or delayed puberty, eunuchoid body habitus (disproportionately long arms and legs), gynecomastia, small and firm testes, low muscle mass, and psychosocial difficulties, and in adults with primary hypogonadism (small testes, low testosterone, high FSH/LH), azoospermia, reduced libido or erectile dysfunction, osteoporosis, and mild cognitive or language difficulties.<ref>{{Cite journal|last=Bojesen|first=Anders|last2=Gravholt|first2=Claus H.|date=2007-04|title=Klinefelter syndrome in clinical practice|url=https://pubmed.ncbi.nlm.nih.gov/17415352|journal=Nature Clinical Practice. Urology|volume=4|issue=4|pages=192–204|doi=10.1038/ncpuro0775|issn=1743-4289|pmid=17415352}}</ref><ref name=":0">{{Cite journal|last=Groth|first=Kristian A.|last2=Skakkebæk|first2=Anne|last3=Høst|first3=Christian|last4=Gravholt|first4=Claus Højbjerg|last5=Bojesen|first5=Anders|date=2013-01|title=Clinical review: Klinefelter syndrome--a clinical update|url=https://pubmed.ncbi.nlm.nih.gov/23118429|journal=The Journal of Clinical Endocrinology and Metabolism|volume=98|issue=1|pages=20–30|doi=10.1210/jc.2012-2382|issn=1945-7197|pmid=23118429}}</ref> | ||
The majority of patients (~80%) with KS are 47,XXY by chromosome analysis, with the remainder being 48,XXXY, 48,XXYY, 49,XXXXY, or mosaic with a normal male cell line.<ref>{{Cite journal|last=Tangshewinsirikul|first=Chayada|last2=Dulyaphat|first2=Wirada|last3=Tim-Aroon|first3=Thipwimol|last4=Parinayok|first4=Rachanee|last5=Chareonsirisuthigul|first5=Takol|last6=Korkiatsakul|first6=Veerawat|last7=Waisayarat|first7=Jariya|last8=Sirisreetreerux|first8=Pokket|last9=Tingthanatikul|first9=Yada|date=2020-12|title=Klinefelter Syndrome Mosaicism 46,XX/47,XXY: A New Case and Literature Review|url=https://pubmed.ncbi.nlm.nih.gov/32733741|journal=Journal of Pediatric Genetics|volume=9|issue=4|pages=221–226|doi=10.1055/s-0040-1713002|issn=2146-4596|pmc=7384885|pmid=32733741}}</ref> | |||
[[File:47,XXY.png|center|thumb|G-banded chromosome analysis of a PHA-stimulated peripheral blood specimen from a patient with Klinefelter Syndrome and a 47,XXY karyotype; Courtesy of Wisconsin Diagnostics Laboratories]] | |||
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==Epidemiology/Prevalence== | ==Epidemiology/Prevalence== | ||
The incidence of KS is approximately 1 in 500 to 1000 male births.<ref name=":0" /><ref>{{Cite journal|last=Berglund|first=Agnethe|last2=Stochholm|first2=Kirstine|last3=Gravholt|first3=Claus Højbjerg|date=2020-06|title=The epidemiology of sex chromosome abnormalities|url=https://pubmed.ncbi.nlm.nih.gov/32506765|journal=American Journal of Medical Genetics. Part C, Seminars in Medical Genetics|volume=184|issue=2|pages=202–215|doi=10.1002/ajmg.c.31805|issn=1552-4876|pmid=32506765}}</ref> However, some studies suggest the prevalence could be as high as 1:600 due to under diagnosis, as many individuals have mild or unnoticed symptoms.<ref>{{Cite journal|last=Bojesen|first=Anders|last2=Juul|first2=Svend|last3=Gravholt|first3=Claus Højbjerg|date=2003-02|title=Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study|url=https://pubmed.ncbi.nlm.nih.gov/12574191|journal=The Journal of Clinical Endocrinology and Metabolism|volume=88|issue=2|pages=622–626|doi=10.1210/jc.2002-021491|issn=0021-972X|pmid=12574191}}</ref> Only about 10% of cases are diagnosed before puberty, and many individuals remain undiagnosed. The median age of diagnosis is in the mid-30s.<ref name=":0" /> There is a significant association with advanced maternal age: around 50-60% of cases result from maternal non-disjunction during meiosis I, while the remaining cases arise from paternal non-disjunction during meiosis II or postzygotic mitotic errors, which are not associated with parental age.<ref>{{Cite journal|last=Thomas|first=N. S.|last2=Hassold|first2=T. J.|date=2003|title=Aberrant recombination and the origin of Klinefelter syndrome|url=https://pubmed.ncbi.nlm.nih.gov/12926525|journal=Human Reproduction Update|volume=9|issue=4|pages=309–317|doi=10.1093/humupd/dmg028|issn=1355-4786|pmid=12926525}}</ref> | The incidence of KS is approximately 1 in 500 to 1000 male births.<ref name=":0" /><ref>{{Cite journal|last=Berglund|first=Agnethe|last2=Stochholm|first2=Kirstine|last3=Gravholt|first3=Claus Højbjerg|date=2020-06|title=The epidemiology of sex chromosome abnormalities|url=https://pubmed.ncbi.nlm.nih.gov/32506765|journal=American Journal of Medical Genetics. Part C, Seminars in Medical Genetics|volume=184|issue=2|pages=202–215|doi=10.1002/ajmg.c.31805|issn=1552-4876|pmid=32506765}}</ref> However, some studies suggest the prevalence could be as high as 1:600 due to under diagnosis, as many individuals have mild or unnoticed symptoms.<ref>{{Cite journal|last=Bojesen|first=Anders|last2=Juul|first2=Svend|last3=Gravholt|first3=Claus Højbjerg|date=2003-02|title=Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study|url=https://pubmed.ncbi.nlm.nih.gov/12574191|journal=The Journal of Clinical Endocrinology and Metabolism|volume=88|issue=2|pages=622–626|doi=10.1210/jc.2002-021491|issn=0021-972X|pmid=12574191}}</ref> Only about 10% of cases are diagnosed before puberty, and many individuals remain undiagnosed. The median age of diagnosis is in the mid-30s.<ref name=":0" /> There is a significant association with advanced maternal age: around 50-60% of cases result from maternal non-disjunction during meiosis I, while the remaining cases arise from paternal non-disjunction during meiosis II or postzygotic mitotic errors, which are not associated with parental age.<ref>{{Cite journal|last=Thomas|first=N. S.|last2=Hassold|first2=T. J.|date=2003|title=Aberrant recombination and the origin of Klinefelter syndrome|url=https://pubmed.ncbi.nlm.nih.gov/12926525|journal=Human Reproduction Update|volume=9|issue=4|pages=309–317|doi=10.1093/humupd/dmg028|issn=1355-4786|pmid=12926525}}</ref> | ||