{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:07:31Z","timestamp":1789027651947,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["NGR2\/2129"],"award-info":[{"award-number":["NGR2\/2129"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Although Klinefelter Syndrome (KS) represents the most common sex chromosome aneuploidy, several gaps in knowledge persist regarding optimal management of individuals with this condition. Individuals with KS can have a diverse phenotype including endocrine, neurodevelopmental, and cardiovascular manifestations.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n To describe the existing KS cohort within\n SDMregistries<\/jats:italic>\n and the development and potential role of the dedicated I\u2010KS module.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Retrospective review of current cases of KS on the\n SDMregistries<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In January 2026, the\n SDMregistries<\/jats:italic>\n platform that consists of dedicated registries for a wide range of rare conditions affecting sex development and maturation included a total of 10, 658 individuals and of these, 777 (7%) individuals from 17 countries had karyotypes consistent with 47, XXY or mosaic forms containing an XXY cell line. Considering those with a 47, XXY alone, the median year of birth was 1994 (range 1939, 2025) resulting in a median current age of 32 (1, 87) years. This therefore represents the largest contemporary international cohort of individuals with KS of varying ages across the lifespan currently available worldwide.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n The\n SDMregistries<\/jats:italic>\n platform offers a unique opportunity to undertake natural history studies as well as evaluations of treatments in KS through the development of a KS specific registry. Such a registry would support evidence\u2010based, personalized care by identifying which interventions work best for specific subgroups and by informing standardized clinical guidelines. This would also assist with care quality improvement, with benchmarking of care and the possibility to accelerate clinical trials by improving patient identification, recruitment, and selection of meaningful outcome measures. Finally, registry data can strengthen advocacy and policy efforts, supporting improved screening, funding, and access to multidisciplinary care.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Continued evaluation of existing data and identification of research priorities remain essential to improving long\u2010term outcomes and quality of life for individuals with KS, with the likelihood of increased ease with the launch of the new I\u2010KS module.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/andr.70392","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:25:10Z","timestamp":1789025110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Need for a Global Registry for Charting the Natural History of Klinefelter Syndrome"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-904X","authenticated-orcid":false,"given":"Malika","family":"Alimussina","sequence":"first","affiliation":[{"name":"Developmental Endocrinology Research Group University of Glasgow Glasgow UK"},{"name":"Office For Rare Conditions Registries University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7235-8501","authenticated-orcid":false,"given":"Joseph","family":"McElvaney","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group University of Glasgow Glasgow UK"},{"name":"Office For Rare Conditions Registries University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Grasemann","sequence":"additional","affiliation":[{"name":"University Medical Center Mainz of the Johannes Gutenberg\u2010University Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-9477","authenticated-orcid":false,"given":"Jillian","family":"Bryce","sequence":"additional","affiliation":[{"name":"Office For Rare Conditions Registries University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7885-7467","authenticated-orcid":false,"given":"Lise","family":"Aksglaede","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction Copenhagen University Hospital \u2010 Rigshospitalet Copenhagen Denmark"},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) Copenhagen University Hospital \u2010 Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5494-2616","authenticated-orcid":false,"given":"Claudia","family":"Boettcher","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Paediatric Endocrinology, Diabetology and Metabolism, Inselspital Bern University Hospital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8987-0246","authenticated-orcid":false,"given":"Lexi","family":"Breen","sequence":"additional","affiliation":[{"name":"University of Lincoln Lincoln UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-4101","authenticated-orcid":false,"given":"Francesco","family":"Carlomagno","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University Rome Italy"},{"name":"Endocrine and Andrological Regional Rare Disease Centre\u2014Endo\u2010ERN Centre \u201cAzienda Ospedaliero\u2010Universitaria Policlinico Umberto I,\u201d Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-0993","authenticated-orcid":false,"given":"Sabine","family":"Hannema","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-5417","authenticated-orcid":false,"given":"Andrea M.","family":"Isidori","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University Rome Italy"},{"name":"Endocrine and Andrological Regional Rare Disease Centre\u2014Endo\u2010ERN Centre \u201cAzienda Ospedaliero\u2010Universitaria Policlinico Umberto I,\u201d Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inas","family":"Mazen","sequence":"additional","affiliation":[{"name":"Cairo National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0405-3401","authenticated-orcid":false,"given":"Anna","family":"Nordenstrom","sequence":"additional","affiliation":[{"name":"Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0689-5549","authenticated-orcid":false,"given":"S. Faisal","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group University of Glasgow Glasgow UK"},{"name":"Office For Rare Conditions Registries University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2662-1684","authenticated-orcid":false,"given":"Angela K.","family":"Lucas\u2010Herald","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group University of Glasgow Glasgow UK"},{"name":"Office For Rare Conditions Registries University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.05.011"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12146"},{"issue":"2","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1210\/jc.2002-021491","article-title":"Prenatal and Postnatal Prevalence of Klinefelter Syndrome: A National Registry Study","volume":"88","author":"Bojesen A.","year":"2003","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"4","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1210\/endrev\/bnaf005","article-title":"New Horizons in Klinefelter Syndrome: Current Evidence, Gaps, and Research Priorities","volume":"46","author":"Lucas\u2010Herald A. K.","year":"2025","journal-title":"Endocrine Reviews"},{"issue":"8","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"e1564","DOI":"10.1210\/clinem\/dgad730","article-title":"From Klinefelter Syndrome to High Grade Aneuploidies: Expanding the Gene\u2010Dosage Effect of Supernumerary X Chromosomes","volume":"109","author":"Spaziani M.","year":"2024","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"issue":"1","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/andr.12909","article-title":"European Academy of Andrology Guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology","volume":"9","author":"Zitzmann M.","year":"2021","journal-title":"Andrology"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.4113"},{"issue":"2","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s12020-025-04376-8","article-title":"A Systematic Review of Core Outcomes Reported in Boys and Men With Klinefelter Syndrome","volume":"90","author":"Frixou M.","year":"2025","journal-title":"Endocrine"},{"issue":"23","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.3390\/ijerph17238743","article-title":"The EuRRECa Project as a Model for Data Access and Governance Policies for Rare Disease Registries That Collect Clinical Outcomes","volume":"17","author":"Ali S. R.","year":"2020","journal-title":"International Journal of Environmental Research and Public Health"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000516178"},{"issue":"1","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/21678707.2023.2241347","article-title":"Real World Data for Rare Diseases Research: The Beginner's Guide to Registries","volume":"11","author":"Pisa F.","year":"2023","journal-title":"Expert Opinion on Orphan Drugs"},{"issue":"4","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/cen.14961","article-title":"The I\u2010CAH Registry: A Platform for International Collaboration for Improving Knowledge and Clinical Care in Congenital Adrenal Hyperplasia","volume":"101","author":"Tseretopoulou X.","year":"2024","journal-title":"Clinical Endocrinology"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad205"},{"issue":"3","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jpurol.2006.03.004","article-title":"Consensus Statement on Management of Intersex Disorders","volume":"2","author":"Hughes I. A.","year":"2006","journal-title":"Journal of Pediatric Urology"},{"issue":"4","key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1159\/000313434","article-title":"The European Disorder of Sex Development Registry: A Virtual Research Environment","volume":"4","author":"Ahmed S.","year":"2010","journal-title":"Sexual Development"},{"issue":"2","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1159\/000524516","article-title":"I\u2010DSD: The First 10 Years","volume":"96","author":"Lucas\u2010Herald A. K.","year":"2023","journal-title":"Hormone Research in Paediatrics"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010017\u20100603\u20107"},{"issue":"4","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.beem.2025.102016","article-title":"Care Quality Improvement in Differences of Sex Development","volume":"39","author":"D\u00f6hnert U.","year":"2025","journal-title":"Best Practice & Research Clinical Endocrinology & Metabolism"},{"issue":"1","key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41572-025-00637-y","article-title":"Differences of Sex Development","volume":"11","author":"Ahmed S. F.","year":"2025","journal-title":"Nature Reviews Disease Primers"},{"issue":"10","key":"e_1_2_12_21_1","doi-asserted-by":"crossref","DOI":"10.1530\/EC-25-0196","article-title":"Continuity of Care in Klinefelter Syndrome: Age\u2010Adapted Modules for Standardized Clinical Data Collection (I\u2010KS)","volume":"14","author":"Grasemann C.","year":"2025","journal-title":"Endocrine Connections"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac056"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70392","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.70392","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:25:13Z","timestamp":1789025113000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.70392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":21,"alternative-id":["10.1111\/andr.70392"],"URL":"https:\/\/doi.org\/10.1111\/andr.70392","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]},"assertion":[{"value":"2026-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"andr.70392"}}