{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:25:32Z","timestamp":1788809132040,"version":"build-2803163510"},"reference-count":81,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T00:00:00Z","timestamp":1358899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>47,XXY (Klinefelter syndrome) is the most frequent sex chromosomal disorder and affects approximately one in 660 newborn boys. The syndrome is characterized by varying degrees of cognitive, social, behavioral, and learning difficulties and in adulthood additionally primary testicular failure with small testes, hypergonadotropic hypogonadism, tall stature, and eunuchoid body proportions. The phenotype is variable ranging from \u201cnear\u2010normal\u201d to a significantly affected individual. In addition, newborns with Klinefelter syndrome generally present with a normal male phenotype and the only consistent clinical finding in KS is small testes, that are most often not identified until after puberty. Decreased awareness of this syndrome among health professionals and a general perception that all patients with 47,XXY exhibit the classic textbook phenotype results in a highly under\u2010diagnosed condition with up to 75% of the patients left undetected. Typically, diagnosis is delayed with the majority of patients identified during fertility workup in adulthood, and only 10% of patients diagnosed prior to puberty. Early detection of this syndrome is recommended in order to offer treatment and intervention at the appropriate ages and stages of development for the purpose of preventing osteopenia\/osteoporosis, metabolic syndrome, and other medical conditions related to hypogonadism and to the XXY as well as minimizing potential learning and psychosocial problems. The aim of this review is to present the clinical aspects of XXY and the age\u2010specific recommendations for medical management. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.c.31349","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T16:47:42Z","timestamp":1358959662000},"page":"55-63","source":"Crossref","is-referenced-by-count":96,"title":["47,XXY Klinefelter syndrome: Clinical characteristics and age\u2010specific recommendations for medical management"],"prefix":"10.1002","volume":"163","author":[{"given":"Lise","family":"Aksglaede","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Link","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Giwercman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels E","family":"Skakkeb\u00e6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Juul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmi039"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2006.02722.x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0310"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2007.120675"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1426"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1207"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2011.02148.x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2011.02246.x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12008"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.12.3976"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2011.02161.x"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.02977.x"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2257"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0365"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021491"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0777"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0697"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-0145"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-010-1354-7"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0367"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2103"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021379"},{"key":"e_1_2_13_24_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3928\/0279-3695-19850101-05","article-title":"Klinefelter syndrome","volume":"23","author":"Cohen FL","year":"1985","journal-title":"J Psychosoc Nurs Ment Health Serv"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1746-1561.1985.tb04089.x"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029733"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1878"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2010.02138.x"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-106-3-"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0575"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000232162"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12687-010-0006-0"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2011.02151.x"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1992.tb02910.x"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.134"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-2-11-615"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031624"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16678-6"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1460075"},{"key":"e_1_2_13_40_1","first-page":"201","article-title":"Follow\u2010up of 25 unselected children with sex chromosome abnormalities to age 12","volume":"26","author":"Nielsen J","year":"1990","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00272390"},{"key":"e_1_2_13_42_1","first-page":"209","article-title":"Sex chromosome abnormalities found among 34,910 newborn children: Results from a 13\u2010year incidence study in Arhus, Denmark","volume":"26","author":"Nielsen J","year":"1990","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33334"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050497"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-54"},{"key":"e_1_2_13_46_1","first-page":"733","article-title":"New roles of SHOX as regulator of target genes","volume":"9","author":"Rappold GA","year":"2012","journal-title":"Pediatr Endocrinol Rev"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-595X(82)80008-X"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.80.2.192"},{"key":"e_1_2_13_49_1","first-page":"1","article-title":"Edinburgh study of growth and development of children with sex chromosome abnormalities. IV","volume":"26","author":"Ratcliffe SG","year":"1990","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087313"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32232"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2006.03.005"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320600503"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/002221949602900208"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198501000-00022"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2009.03.006"},{"key":"e_1_2_13_57_1","first-page":"325","article-title":"Growth and body proportions in 54 boys and men with Klinefelter's syndrome","volume":"29","author":"Schibler D","year":"1974","journal-title":"Helv Paediatr Acta"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)90878-1"},{"key":"e_1_2_13_59_1","first-page":"387","article-title":"Body proportions and androgenicity in relation to plasma testosterone levels in Klinefelter's syndrome","volume":"77","author":"Smals AG","year":"1974","journal-title":"Acta Endocrinol (Copenh)"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000182402"},{"key":"e_1_2_13_61_1","first-page":"561","article-title":"Klinefelter's syndrome: Clinical and hormonal aspects","volume":"28","author":"Stewart JS","year":"1959","journal-title":"Q J Med"},{"key":"e_1_2_13_62_1","first-page":"1","article-title":"Summary of clinical findings of children with 47,XXY,47,XYY, and 47,XXX karyotypes","volume":"18","author":"Stewart DA","year":"1982","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2011-000650"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.2001.6520177.x"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1077"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji240"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(59)90558-6"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(76)80620-8"},{"key":"e_1_2_13_69_1","first-page":"779","article-title":"Metabolic syndrome X: A review","volume":"16","author":"Timar O","year":"2000","journal-title":"Can J Cardiol"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00442070"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/11.suppl_4.1"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.105.008961"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.02.020"},{"key":"e_1_2_13_74_1","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1017\/S1355617707071044","article-title":"What it is said versus how it is said: Comprehension of affective prosody in men with Klinefelter (47,XXY) syndrome","volume":"13","author":"Van RS","year":"2007","journal-title":"J Int Neuropsychol Soc"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2008.02.001"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-008-0542-1"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031725"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0669"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000219386.31398.c3"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1892"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.10.019"},{"key":"e_1_2_13_82_1","first-page":"5","article-title":"Klinefelter's syndrome, a clinical and cytogenetic study in twenty\u2010four cases","volume":"113","author":"Zuppinger K","year":"1967","journal-title":"Acta Endocrinol (Copenh)"}],"container-title":["American Journal of Medical Genetics Part C: Seminars in Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.c.31349","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.31349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T06:20:20Z","timestamp":1694672420000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.31349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,23]]},"references-count":81,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,2,15]]}},"alternative-id":["10.1002\/ajmg.c.31349"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.31349","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"value":"1552-4868","type":"print"},{"value":"1552-4876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,23]]}}}