{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:05:52Z","timestamp":1787940352742,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Research to guide clinicians in the management of the devastating regression which can affect adolescents and young adults with Down syndrome is limited. A multi\u2010site, international, longitudinal cohort of individuals with a clinical diagnosis of Unexplained Regression in Down syndrome (URDS) was collated through seven Down syndrome clinics. Tiered medical evaluation, a 28\u2010item core symptom list, and interim management are described naturalistically. Improvement\u2014defined by the percentage of baseline function on a Parent\u2010reported Functional Score, overall improvement in symptoms on a Clinician\u2010administered Functional Assessment, or report of management type being associated with improvement\u2014was analyzed. Improvement rates using ECT, IVIG, and others were compared. Across seven clinics, 51 patients with URDS had regression at age 17.6\u2009years, on average, and showed an average 14.1 out of 28 symptoms. Longitudinal improvement in function was achieved in many patients and the medical management, types of treatment, and their impact on function are described. Management with intravenous immunoglobulin (IVIG) was significantly associated with higher rate of improvement in symptoms at the next visit (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.001). Our longitudinal data demonstrates that URDS is treatable, with various forms of clinical management and has a variable course. The data suggests that IVIG may be an effective treatment in some individuals. Our description of the management approaches used in this cohort lays the groundwork for future research, such as development of standardized objective outcome measure and creation of a clinical practice guideline for URDS.<\/jats:p>","DOI":"10.1002\/ajmg.a.62922","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T11:13:44Z","timestamp":1659611624000},"page":"3049-3062","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Unexplained regression in Down syndrome: Management of 51 patients in an international patient database"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4172-0288","authenticated-orcid":false,"given":"Stephanie L.","family":"Santoro","sequence":"first","affiliation":[{"name":"Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole T.","family":"Baumer","sequence":"additional","affiliation":[{"name":"Department of Neurology Harvard Medical School  Boston Massachusetts USA"},{"name":"Boston Children's Hospital Down Syndrome Program Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Cornacchia","sequence":"additional","affiliation":[{"name":"Geisinger Health System  Danville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Franklin","sequence":"additional","affiliation":[{"name":"Mater Research Institute\u2010University of Queensland The University of Queensland  South Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0974-3209","authenticated-orcid":false,"given":"Sarah J.","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Haugen","sequence":"additional","affiliation":[{"name":"Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-9776","authenticated-orcid":false,"given":"Margaret A.","family":"Hojlo","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital Down Syndrome Program Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Horick","sequence":"additional","affiliation":[{"name":"Biostatistics Center Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya S.","family":"Kishnani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7905-871X","authenticated-orcid":false,"given":"Kavita","family":"Krell","sequence":"additional","affiliation":[{"name":"Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"McCormick","sequence":"additional","affiliation":[{"name":"Down Syndrome Center of Western Pennsylvania UPMC Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L.","family":"Milliken","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital Down Syndrome Program Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas M.","family":"Oreskovic","sequence":"additional","affiliation":[{"name":"Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine G.","family":"Pawlowski","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital Down Syndrome Program Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Sargado","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"},{"name":"Boston Children's Hospital Down Syndrome Program Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Torres","sequence":"additional","affiliation":[{"name":"Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Valentini","sequence":"additional","affiliation":[{"name":"Pediatric and Infectious Disease Unit Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishore","family":"Vellody","sequence":"additional","affiliation":[{"name":"Down Syndrome Center of Western Pennsylvania UPMC Children's Hospital of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5232-9882","authenticated-orcid":false,"given":"Brian G.","family":"Skotko","sequence":"additional","affiliation":[{"name":"Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S32767"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-495-7"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14127"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2015.09.002"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-386495-6.00007-2"},{"key":"e_1_2_12_7_1","unstructured":"Down Syndrome Medical Interest Group \u2010 USA \u2010 Home. Accessed January 4 2019.https:\/\/www.dsmig-usa.org\/"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S77307"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.621637"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37674"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCT.0b013e31821d37c6"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38219"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37267"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S210613"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci7060057"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S147897"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0790966700007205"},{"issue":"2","key":"e_1_2_12_19_1","first-page":"219","article-title":"Personality in mongolism with special reference to the incidence of catatonic psychosis","volume":"51","author":"Rollin H. R.","year":"1946","journal-title":"American Journal of Mental Deficiency"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-2939"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0706-8"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37879"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.08m04872gre"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2015.3097"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2015.06.006"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073814554654"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62922","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62922","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62922","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:43:29Z","timestamp":1708497809000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,4]]},"references-count":25,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/ajmg.a.62922"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62922","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,4]]},"assertion":[{"value":"2022-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}