GTS5:Klinefelter syndrome - Revision history

Richard.Glen at 00:54, 26 February 2026

2026-02-26T00:54:39Z

← Older revision		Revision as of 19:54, 25 February 2026
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	==References==		==References==
	(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>		(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
			<references />

	==Notes==		==Notes==
	<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership\|''<u>Associate Editor</u>'']] or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.		<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership\|''<u>Associate Editor</u>'']] or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
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	[[Category:GTS5]]		[[Category:GTS5]]
	[[Category:DISEASE]]		[[Category:DISEASE]]
	~~<references />~~

Bailey.Glen at 21:16, 25 May 2025

2025-05-25T21:16:08Z

← Older revision		Revision as of 16:16, 25 May 2025
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	==Related Terminology==		==Related Terminology==
	~~<span style="color:#0070C0">(''Instructions: This table will have the related terminology from the WHO book <u>autocompleted</u>.)''</span>~~
	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+
	\|Acceptable		\|Acceptable
	\|47,XXY ~~Syndrome~~		\|47,XXY syndrome
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|N/A
	\|}		\|}

Bailey.Glen at 19:58, 25 May 2025

2025-05-25T19:58:03Z

← Older revision		Revision as of 14:58, 25 May 2025
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			[[GTS5:Table_of_Contents\|Genetic Tumour Syndromes (Who Classification, 5th ed.)]]
	{{Under Construction}}		{{Under Construction}}
	<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>		<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
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	Kathleen M. Bone, PhD, Medical College of Wisconsin		Kathleen M. Bone, PhD, Medical College of Wisconsin
	==WHO Classification of Disease==		==WHO Classification of Disease==
	~~<span style="color:#0070C0">(''Instructions: This table’s content from the WHO book will be <u>autocompleted</u>.'')</span>~~
	{\| class="wikitable"		{\| class="wikitable"
	!Structure		!Structure
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	\|-		\|-
	\|Book		\|Book
	\|		\|Genetic Tumour Syndromes (5th ed.)
	\|-		\|-
	\|Category		\|Category
	\|		\|DNA repair and genomic stability
	\|-		\|-
	\|Family		\|Family
	\|		\|Chromosomal non-dysjunction (aneuploidy) syndromes
	\|-		\|-
	\|Type		\|Type
	\|		\|Klinefelter syndrome
	\|-		\|-
	\|Subtype(s)		\|Subtype(s)
	\|		\|N/A
	\|}		\|}

	==Related Terminology==		==Related Terminology==
	<span style="color:#0070C0">(''Instructions: This table will have the related terminology from the WHO book <u>autocompleted</u>.)''</span>		<span style="color:#0070C0">(''Instructions: This table will have the related terminology from the WHO book <u>autocompleted</u>.)''</span>

Kathleen.Bone: /* Epidemiology/Prevalence */

2025-03-10T20:33:53Z

Epidemiology/Prevalence

← Older revision		Revision as of 15:33, 10 March 2025
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	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>

	KS also carriers an increased risk for breast cancer and extragonadal germ cell tumors. Males with KS have a 20-30-fold increased risk of developing breast cancer over the average male population risk of approximately 1 in 726.<ref>{{Cite journal\|last=Swerdlow\|first=Anthony J.\|last2=Schoemaker\|first2=Minouk J.\|last3=Higgins\|first3=Craig D.\|last4=Wright\|first4=Alan F.\|last5=Jacobs\|first5=Patricia A.\|last6=UK Clinical Cytogenetics Group\|date=2005-08-17\|title=Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study\|url=https://pubmed.ncbi.nlm.nih.gov/16106025\|journal=Journal of the National Cancer Institute\|volume=97\|issue=16\|pages=1204–1210\|doi=10.1093/jnci/dji240\|issn=1460-2105\|pmid=16106025}}</ref> There is also an increased incidence of mediastinal germ cell tumors (M-GCTs) in KS patients, which can lead to precocious puberty due to human chorionic gonadotropin (hCG)-producing M-GCTs.<ref>{{Cite journal\|last=Hasle\|first=H.\|last2=Jacobsen\|first2=B. B.\|last3=Asschenfeldt\|first3=P.\|last4=Andersen\|first4=K.\|date=1992-10\|title=Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature\|url=https://pubmed.ncbi.nlm.nih.gov/1425792\|journal=European Journal of Pediatrics\|volume=151\|issue=10\|pages=735–739\|doi=10.1007/BF01959079\|issn=0340-6199\|pmid=1425792}}</ref><ref>{{Cite journal\|last=Völkl\|first=Thomas M. K.\|last2=Langer\|first2=Thorsten\|last3=Aigner\|first3=Thomas\|last4=Greess\|first4=Holger\|last5=Beck\|first5=Jörn D.\|last6=Rauch\|first6=Anita M.\|last7=Dörr\|first7=Helmuth G.\|date=2006-03-01\|title=Klinefelter syndrome and mediastinal germ cell tumors\|url=https://pubmed.ncbi.nlm.nih.gov/16470792\|journal=American Journal of Medical Genetics. Part A\|volume=140\|issue=5\|pages=471–481\|doi=10.1002/ajmg.a.31103\|issn=1552-4825\|pmid=16470792}}</ref> The pathophysiology is unclear, but is thought to be related to genes the extra X chromosome.<ref>{{Cite journal\|last=Rapley\|first=E. A.\|last2=Crockford\|first2=G. P.\|last3=Teare\|first3=D.\|last4=Biggs\|first4=P.\|last5=Seal\|first5=S.\|last6=Barfoot\|first6=R.\|last7=Edwards\|first7=S.\|last8=Hamoudi\|first8=R.\|last9=Heimdal\|first9=K.\|date=2000-02\|title=Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours\|url=https://pubmed.ncbi.nlm.nih.gov/10655070\|journal=Nature Genetics\|volume=24\|issue=2\|pages=197–200\|doi=10.1038/72877\|issn=1061-4036\|pmid=10655070}}</ref>		KS also carriers an increased risk for breast cancer and extragonadal germ cell tumors. Males with KS have a 20-30-fold increased risk of developing breast cancer over the average male population risk of approximately 1 in 726.<ref>{{Cite journal\|last=Swerdlow\|first=Anthony J.\|last2=Schoemaker\|first2=Minouk J.\|last3=Higgins\|first3=Craig D.\|last4=Wright\|first4=Alan F.\|last5=Jacobs\|first5=Patricia A.\|last6=UK Clinical Cytogenetics Group\|date=2005-08-17\|title=Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study\|url=https://pubmed.ncbi.nlm.nih.gov/16106025\|journal=Journal of the National Cancer Institute\|volume=97\|issue=16\|pages=1204–1210\|doi=10.1093/jnci/dji240\|issn=1460-2105\|pmid=16106025}}</ref> There is also an increased incidence of mediastinal germ cell tumors (M-GCTs) in KS patients, which can lead to precocious puberty due to human chorionic gonadotropin (hCG)-producing M-GCTs.<ref>{{Cite journal\|last=Hasle\|first=H.\|last2=Jacobsen\|first2=B. B.\|last3=Asschenfeldt\|first3=P.\|last4=Andersen\|first4=K.\|date=1992-10\|title=Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature\|url=https://pubmed.ncbi.nlm.nih.gov/1425792\|journal=European Journal of Pediatrics\|volume=151\|issue=10\|pages=735–739\|doi=10.1007/BF01959079\|issn=0340-6199\|pmid=1425792}}</ref><ref>{{Cite journal\|last=Völkl\|first=Thomas M. K.\|last2=Langer\|first2=Thorsten\|last3=Aigner\|first3=Thomas\|last4=Greess\|first4=Holger\|last5=Beck\|first5=Jörn D.\|last6=Rauch\|first6=Anita M.\|last7=Dörr\|first7=Helmuth G.\|date=2006-03-01\|title=Klinefelter syndrome and mediastinal germ cell tumors\|url=https://pubmed.ncbi.nlm.nih.gov/16470792\|journal=American Journal of Medical Genetics. Part A\|volume=140\|issue=5\|pages=471–481\|doi=10.1002/ajmg.a.31103\|issn=1552-4825\|pmid=16470792}}</ref> The pathophysiology is unclear, but is thought to be related to genes on the extra X chromosome.<ref>{{Cite journal\|last=Rapley\|first=E. A.\|last2=Crockford\|first2=G. P.\|last3=Teare\|first3=D.\|last4=Biggs\|first4=P.\|last5=Seal\|first5=S.\|last6=Barfoot\|first6=R.\|last7=Edwards\|first7=S.\|last8=Hamoudi\|first8=R.\|last9=Heimdal\|first9=K.\|date=2000-02\|title=Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours\|url=https://pubmed.ncbi.nlm.nih.gov/10655070\|journal=Nature Genetics\|volume=24\|issue=2\|pages=197–200\|doi=10.1038/72877\|issn=1061-4036\|pmid=10655070}}</ref>
	==Genetic Abnormalities: Germline==		==Genetic Abnormalities: Germline==
	Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span>		Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span>

Kathleen.Bone: /* Definition/Description of Disease */

2025-03-10T20:32:11Z

Definition/Description of Disease

← Older revision		Revision as of 15:32, 10 March 2025
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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%-90%) with KS are 47,XXY by chromosome analysis, with the remainder being 48,XXXY, 48,XXYY, 49,XXXXY, or mosaic with a normal 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><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> While the majority of mosaic KS patients have a normal male cell line, individuals with a normal female karyotype have also been described. Mosaic individuals typically present with a more variability clinical phenotype, and are often diagnosed due to infertility.<ref>{{Cite journal\|last=Samplaski\|first=Mary K.\|last2=Lo\|first2=Kirk C.\|last3=Grober\|first3=Ethan D.\|last4=Millar\|first4=Adam\|last5=Dimitromanolakis\|first5=Apostolos\|last6=Jarvi\|first6=Keith A.\|date=2014-04\|title=Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients\|url=https://pubmed.ncbi.nlm.nih.gov/24502895\|journal=Fertility and Sterility\|volume=101\|issue=4\|pages=950–955\|doi=10.1016/j.fertnstert.2013.12.051\|issn=1556-5653\|pmid=24502895}}</ref> Individuals with a normal female cell line may have ambiguous genitalia and the presence of ovotestes.<ref>{{Cite journal\|last=Guess\|first=Tiffany\|last2=Wheeler\|first2=Ferrin C.\|last3=Yenamandra\|first3=Ashwini\|last4=Schilit\|first4=Samantha L. P.\|last5=Anderson\|first5=Hannah S.\|last6=Bone\|first6=Kathleen M.\|last7=Carstens\|first7=Billie\|last8=Conlin\|first8=Laura\|last9=Dulik\|first9=Matthew C.\|date=2024-10\|title=A multicenter analysis of individuals with a 47,XXY/46,XX karyotype\|url=https://pubmed.ncbi.nlm.nih.gov/39011769\|journal=Genetics in Medicine: Official Journal of the American College of Medical Genetics\|volume=26\|issue=10\|pages=101212\|doi=10.1016/j.gim.2024.101212\|issn=1530-0366\|pmid=39011769}}</ref>		The majority of patients (~80%-90%) with KS are 47,XXY by chromosome analysis, with the remainder being 48,XXXY, 48,XXYY, 49,XXXXY, or mosaic with a normal 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><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> While the majority of mosaic KS patients have a normal male cell line, individuals with a normal female karyotype have also been described. Mosaic individuals typically present with a more variability clinical phenotype, and are often diagnosed due to infertility.<ref>{{Cite journal\|last=Samplaski\|first=Mary K.\|last2=Lo\|first2=Kirk C.\|last3=Grober\|first3=Ethan D.\|last4=Millar\|first4=Adam\|last5=Dimitromanolakis\|first5=Apostolos\|last6=Jarvi\|first6=Keith A.\|date=2014-04\|title=Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients\|url=https://pubmed.ncbi.nlm.nih.gov/24502895\|journal=Fertility and Sterility\|volume=101\|issue=4\|pages=950–955\|doi=10.1016/j.fertnstert.2013.12.051\|issn=1556-5653\|pmid=24502895}}</ref> Individuals with a normal female cell line may have ambiguous genitalia and the presence of ovotestes.<ref>{{Cite journal\|last=Guess\|first=Tiffany\|last2=Wheeler\|first2=Ferrin C.\|last3=Yenamandra\|first3=Ashwini\|last4=Schilit\|first4=Samantha L. P.\|last5=Anderson\|first5=Hannah S.\|last6=Bone\|first6=Kathleen M.\|last7=Carstens\|first7=Billie\|last8=Conlin\|first8=Laura\|last9=Dulik\|first9=Matthew C.\|date=2024-10\|title=A multicenter analysis of individuals with a 47,XXY/46,XX karyotype\|url=https://pubmed.ncbi.nlm.nih.gov/39011769\|journal=Genetics in Medicine: Official Journal of the American College of Medical Genetics\|volume=26\|issue=10\|pages=101212\|doi=10.1016/j.gim.2024.101212\|issn=1530-0366\|pmid=39011769}}</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]]		[[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]]

Kathleen.Bone: /* Definition/Description of Disease */

2025-03-10T20:28:41Z

Definition/Description of Disease

← Older revision		Revision as of 15:28, 10 March 2025
Line 37:		Line 37:
	==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>		The majority of patients (~80%-90%) with KS are 47,XXY by chromosome analysis, with the remainder being 48,XXXY, 48,XXYY, 49,XXXXY, or mosaic with a normal 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><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> While the majority of mosaic KS patients have a normal male cell line, individuals with a normal female karyotype have also been described. Mosaic individuals typically present with a more variability clinical phenotype, and are often diagnosed due to infertility.<ref>{{Cite journal\|last=Samplaski\|first=Mary K.\|last2=Lo\|first2=Kirk C.\|last3=Grober\|first3=Ethan D.\|last4=Millar\|first4=Adam\|last5=Dimitromanolakis\|first5=Apostolos\|last6=Jarvi\|first6=Keith A.\|date=2014-04\|title=Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients\|url=https://pubmed.ncbi.nlm.nih.gov/24502895\|journal=Fertility and Sterility\|volume=101\|issue=4\|pages=950–955\|doi=10.1016/j.fertnstert.2013.12.051\|issn=1556-5653\|pmid=24502895}}</ref> Individuals with a normal female cell line may have ambiguous genitalia and the presence of ovotestes.<ref>{{Cite journal\|last=Guess\|first=Tiffany\|last2=Wheeler\|first2=Ferrin C.\|last3=Yenamandra\|first3=Ashwini\|last4=Schilit\|first4=Samantha L. P.\|last5=Anderson\|first5=Hannah S.\|last6=Bone\|first6=Kathleen M.\|last7=Carstens\|first7=Billie\|last8=Conlin\|first8=Laura\|last9=Dulik\|first9=Matthew C.\|date=2024-10\|title=A multicenter analysis of individuals with a 47,XXY/46,XX karyotype\|url=https://pubmed.ncbi.nlm.nih.gov/39011769\|journal=Genetics in Medicine: Official Journal of the American College of Medical Genetics\|volume=26\|issue=10\|pages=101212\|doi=10.1016/j.gim.2024.101212\|issn=1530-0366\|pmid=39011769}}</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]]		[[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]]
	<br />		<br />

Kathleen.Bone at 20:19, 10 March 2025

2025-03-10T20:19:58Z

← Older revision		Revision as of 15:19, 10 March 2025
Line 36:		Line 36:

	==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]]
			<br />
	==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>

Kathleen.Bone at 20:05, 10 March 2025

2025-03-10T20:05:33Z

← Older revision		Revision as of 15:05, 10 March 2025
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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>

			KS also carriers an increased risk for breast cancer and extragonadal germ cell tumors. Males with KS have a 20-30-fold increased risk of developing breast cancer over the average male population risk of approximately 1 in 726.<ref>{{Cite journal\|last=Swerdlow\|first=Anthony J.\|last2=Schoemaker\|first2=Minouk J.\|last3=Higgins\|first3=Craig D.\|last4=Wright\|first4=Alan F.\|last5=Jacobs\|first5=Patricia A.\|last6=UK Clinical Cytogenetics Group\|date=2005-08-17\|title=Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study\|url=https://pubmed.ncbi.nlm.nih.gov/16106025\|journal=Journal of the National Cancer Institute\|volume=97\|issue=16\|pages=1204–1210\|doi=10.1093/jnci/dji240\|issn=1460-2105\|pmid=16106025}}</ref> There is also an increased incidence of mediastinal germ cell tumors (M-GCTs) in KS patients, which can lead to precocious puberty due to human chorionic gonadotropin (hCG)-producing M-GCTs.<ref>{{Cite journal\|last=Hasle\|first=H.\|last2=Jacobsen\|first2=B. B.\|last3=Asschenfeldt\|first3=P.\|last4=Andersen\|first4=K.\|date=1992-10\|title=Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature\|url=https://pubmed.ncbi.nlm.nih.gov/1425792\|journal=European Journal of Pediatrics\|volume=151\|issue=10\|pages=735–739\|doi=10.1007/BF01959079\|issn=0340-6199\|pmid=1425792}}</ref><ref>{{Cite journal\|last=Völkl\|first=Thomas M. K.\|last2=Langer\|first2=Thorsten\|last3=Aigner\|first3=Thomas\|last4=Greess\|first4=Holger\|last5=Beck\|first5=Jörn D.\|last6=Rauch\|first6=Anita M.\|last7=Dörr\|first7=Helmuth G.\|date=2006-03-01\|title=Klinefelter syndrome and mediastinal germ cell tumors\|url=https://pubmed.ncbi.nlm.nih.gov/16470792\|journal=American Journal of Medical Genetics. Part A\|volume=140\|issue=5\|pages=471–481\|doi=10.1002/ajmg.a.31103\|issn=1552-4825\|pmid=16470792}}</ref> The pathophysiology is unclear, but is thought to be related to genes the extra X chromosome.<ref>{{Cite journal\|last=Rapley\|first=E. A.\|last2=Crockford\|first2=G. P.\|last3=Teare\|first3=D.\|last4=Biggs\|first4=P.\|last5=Seal\|first5=S.\|last6=Barfoot\|first6=R.\|last7=Edwards\|first7=S.\|last8=Hamoudi\|first8=R.\|last9=Heimdal\|first9=K.\|date=2000-02\|title=Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours\|url=https://pubmed.ncbi.nlm.nih.gov/10655070\|journal=Nature Genetics\|volume=24\|issue=2\|pages=197–200\|doi=10.1038/72877\|issn=1061-4036\|pmid=10655070}}</ref>
	==Genetic Abnormalities: Germline==		==Genetic Abnormalities: Germline==
	Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span>		Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span>
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	[[Category:GTS5]]		[[Category:GTS5]]
	[[Category:DISEASE]]		[[Category:DISEASE]]
			<references />

Kathleen.Bone at 19:56, 10 March 2025

2025-03-10T19:56:04Z

← Older revision		Revision as of 14:56, 10 March 2025
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	==Definition/Description of Disease==		==Definition/Description of Disease==
	~~Put your text here~~ <~~span style~~="~~color~~:~~#0070C0~~">~~(''Instructions~~: ~~Include~~ a ~~brief general~~ clinical ~~description, diagnostic criteria, and differential diagnosis if applicable~~. ~~Include disease context relative to other WHO classification categories, i~~.e. ~~describe any information relevant to the genetic aspects~~ of ~~the disease from all WHO classification books in which the syndrome is described~~.~~'')~~</~~span~~>		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>
	==Epidemiology/Prevalence==		==Epidemiology/Prevalence==
	~~Put your text here~~		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>
	==Genetic Abnormalities: Germline==		==Genetic Abnormalities: Germline==
	Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span>		Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe germline alteration(s) that cause the syndrome. In the notes, include additional details about most common mutations including founder mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetics-related information. If multiple causes of the syndrome, include relative prevalence of genetic contributions to that syndrome. Please include references throughout the table. Do not delete the table.'')</span>

Kathleen.Bone at 19:19, 10 March 2025

2025-03-10T19:19:33Z

← Older revision		Revision as of 14:19, 10 March 2025
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	<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>		<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
	==Primary Author(s)*==		==Primary Author(s)*==
	~~Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith~~, PhD~~) </span>~~		Kathleen M. Bone, PhD, Medical College of Wisconsin
	==WHO Classification of Disease==		==WHO Classification of Disease==
	<span style="color:#0070C0">(''Instructions: This table’s content from the WHO book will be <u>autocompleted</u>.'')</span>		<span style="color:#0070C0">(''Instructions: This table’s content from the WHO book will be <u>autocompleted</u>.'')</span>
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	\|+		\|+
	\|Acceptable		\|Acceptable
	\|		\|47,XXY Syndrome
	\|-		\|-
	\|Not Recommended		\|Not Recommended
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	Prior Author(s):		Prior Author(s):
	[[Category:GTS5]][[Category:DISEASE]]		[[Category:GTS5]]
			[[Category:DISEASE]]