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KS subjects are typically tall, with small and firm testes, gynecomastia, broad hips, and sparse body hair, although a less evident presentation is also possible. KS is also characterized by a high prevalence of hypogonadism, metabolic syndrome (MetS) and cardiovascular disease. The aim of this article is to systematically review metabolic and the cardiovascular risk factors in KS patients. Hypogonadism has an important role in the pathogenesis of the changes in body composition (particularly visceral obesity) and hence of insulin resistance and MetS, but the association between KS and MetS may go beyond hypogonadism alone. From childhood, KS patients may show an increase in visceral fat with a reduction in lean body mass and an increase in glucose and impaired fat metabolism. Their increased incidence of congenital anomalies, epicardial adipose tissue, and thromboembolic disease suggests they have a higher risk of cardiovascular disease. There is conflicting evidence on the effects of testosterone therapy on body composition and metabolism.<\/jats:p>","DOI":"10.1002\/ajmg.c.31792","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T11:09:07Z","timestamp":1590491347000},"page":"334-343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Metabolic and cardiovascular risk factors in Klinefelter syndrome"],"prefix":"10.1002","volume":"184","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5645-5766","authenticated-orcid":false,"given":"Matteo","family":"Spaziani","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology Sapienza University of Rome  Rome Italy"},{"name":"Centre for Rare Diseases, Policlinico Umberto I  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio F.","family":"Radicioni","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology Sapienza University of Rome  Rome Italy"},{"name":"Centre for Rare Diseases, Policlinico Umberto I  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199704)17:4<363::AID-PD79>3.0.CO;2-O"},{"issue":"8","key":"e_1_2_10_3_1","first-page":"520","article-title":"Hypertrophic cardiomyopathy in a patient of Klinefelter syndrome: A rare association","volume":"9","author":"Ahmed S.","year":"2009","journal-title":"Journal of the College of Physicians and Surgeons\u2010Pakistan"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2007.120675"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03211.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e32833894eb"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)39135-X"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2011.01223.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaq016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0697"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021491"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-0145"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1981.tb00709.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20190412"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.10.054"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(89)90014-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2019.08.011"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-19-0433"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2834"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c170042"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12770"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0447"},{"issue":"1","key":"e_1_2_10_23_1","first-page":"176","article-title":"Effects of Oxandrolone on Cardiometabolic health in boys with Klinefelter syndrome: A randomized controlled trial","volume":"102","author":"Davis S. 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