{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T18:22:13Z","timestamp":1771006933210,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR)","doi-asserted-by":"publisher","award":["MOP-313331"],"award-info":[{"award-number":["MOP-313331"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR)","doi-asserted-by":"publisher","award":["MOP-111238"],"award-info":[{"award-number":["MOP-111238"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The 22q11.2 microdeletion and its associated conditions could affect reproductive outcomes but there is limited information on this important area. We investigated reproductive outcomes in a sample of 368 adults with typical 22q11.2 deletions (median age 32.8, range 17.9\u201376.3 years; 195 females), and without moderate-severe intellectual disability, who were followed prospectively. We examined all reproductive outcomes and possible effects of diagnosis as a transmitting parent on these outcomes. We used logistic regression to investigate factors relevant to reproductive fitness (liveborn offspring). There were 63 (17.1%) individuals with 157 pregnancy outcomes, 94 (60.3%) of which involved live births. Amongst the remainder involving a form of loss, were seven (5.77%) stillbirths, significantly greater than population norms (p &lt; 0.0001). For 35 (55.6%) individuals, diagnosis of 22q11.2 deletion syndrome (22q11.2DS) followed diagnosis of an offspring, with disproportionately fewer individuals had major congenital heart disease (CHD) in that transmitting parent subgroup. The regression model indicated that major CHD, in addition to previously identified factors, was a significant independent predictor of reduced reproductive fitness. There was evidence of persisting diagnostic delay and limited prenatal genetic testing. The findings indicate that pregnancy loss is an important health issue for adults with 22q11.2DS. CHD and\/or its absence is a factor to consider in reproductive outcome research. Further studies are warranted to better appreciate factors that may contribute to reproductive outcomes, including technological advances. The results suggest the need for ongoing efforts to provide optimal education and supports to individuals with 22q11.2DS, and their clinicians, around reproductive issues and early diagnosis.<\/jats:p>","DOI":"10.3390\/genes13112126","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:31:27Z","timestamp":1668565887000},"page":"2126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Reproductive Outcomes in Adults with 22q11.2 Deletion Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Lisa D.","family":"Palmer","sequence":"first","affiliation":[{"name":"The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zo\u00eb","family":"McManus","sequence":"additional","affiliation":[{"name":"Undergraduate Medical Education, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Heung","sequence":"additional","affiliation":[{"name":"The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"McAlpine","sequence":"additional","affiliation":[{"name":"Undergraduate Medical Education, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Blagojevic","sequence":"additional","affiliation":[{"name":"The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Corral","sequence":"additional","affiliation":[{"name":"The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-7279","authenticated-orcid":false,"given":"Anne S.","family":"Bassett","sequence":"additional","affiliation":[{"name":"The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"},{"name":"Toronto General Hospital Research Institute, Toronto, ON M5G 2C4, Canada"},{"name":"Campbell Family Mental Health Research Institute, Toronto, ON M5G 2C1, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","first-page":"E802","article-title":"Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: A cross-sectional analysis from population-based newborn screening","volume":"9","author":"Blagojevic","year":"2021","journal-title":"Can. Med. Assoc. J. Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15071","DOI":"10.1038\/nrdp.2015.71","article-title":"22q11.2 deletion syndrome","volume":"1","author":"Sullivan","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/jmg.30.10.813","article-title":"Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: Implications for genetic counselling and prenatal diagnosis","volume":"30","author":"Driscoll","year":"1993","journal-title":"J. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/ajmg.a.38645","article-title":"Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome","volume":"176","author":"Palmer","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1136\/jmedgenet-2011-100440","article-title":"Sex differences in reproductive fitness contribute to preferential maternal transmission of 22q11.2 deletions","volume":"48","author":"Costain","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1007\/s10897-014-9811-7","article-title":"Reproductive Health Issues for Adults with a Common Genomic Disorder: 22q11.2 Deletion Syndrome","volume":"24","author":"Chan","year":"2015","journal-title":"J. Genet. Couns."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/jar.12927","article-title":"Sexual knowledge and behaviour in 22q11.2 deletion syndrome, a complex care condition","volume":"35","author":"Palmer","year":"2022","journal-title":"J. Appl. Res. Intellect. Disabil."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/gim.2014.175","article-title":"Practical guidelines for managing adults with 22q11.2 deletion syndrome","volume":"17","author":"Fung","year":"2015","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100528","DOI":"10.1016\/j.eclinm.2020.100528","article-title":"22q11.2 microdeletion and increased risk for type 2 diabetes","volume":"26","author":"Van","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41436-019-0603-1","article-title":"A genetic model for multimorbidity in young adults","volume":"22","author":"Malecki","year":"2020","journal-title":"Genet. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ajmg.a.30984","article-title":"Clinical features of 78 adults with 22q11 Deletion Syndrome","volume":"138","author":"Bassett","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1136\/hrt.2007.122671","article-title":"Comorbidity, healthcare utilisation and process of care measures in patients with congenital heart disease in the UK: Cross-sectional, population-based study with case-control analysis","volume":"94","author":"Billett","year":"2008","journal-title":"Heart"},{"key":"ref_13","unstructured":"Statistics Canada (2022, October 10). Live Births and Fetal Deaths (Stillbirths), by Type of Birth (Single or Multiple). Available online: https:\/\/www150.statcan.gc.ca\/t1\/tbl1\/en\/tv.action?pid=1310042801."},{"key":"ref_14","unstructured":"Harrell, F.E. (2022). rms: Regression Modeling Strategies. R Package Version 6.3-0, Springer."},{"key":"ref_15","first-page":"7","article-title":"Diagnostic Checking in Regression Relationships","volume":"2","author":"Zeileis","year":"2022","journal-title":"R News"},{"key":"ref_16","unstructured":"Canadian Institute for Health Information (2022). Induced Abortions Reported in Canada in 2020, CIHI."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/S1701-2163(16)35269-0","article-title":"A review of therapeutic abortions and related areas of concern in Canada","volume":"34","author":"Sabourin","year":"2012","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1002\/ajmg.a.38555","article-title":"Higher adaptive functioning and lower rate of psychotic comorbidity in married versus unmarried individuals with 22q11.2 deletion syndrome","volume":"176","author":"Mosheva","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1056\/NEJMoa1201569","article-title":"Karyotype versus microarray testing for genetic abnormalities after stillbirth","volume":"367","author":"Reddy","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/uog.14866","article-title":"Diagnostic utility of microarray testing of pregnancy losses","volume":"46","author":"Rosenfeld","year":"2015","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13039-017-0308-6","article-title":"Incidence of the 22q11.2 deletion in a large cohort of miscarriage samples","volume":"10","author":"Maisenbacher","year":"2017","journal-title":"Mol. Cytogenet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/uog.20412","article-title":"Systematic analysis of copy-number variations associated with early pregnancy loss","volume":"55","author":"Wang","year":"2020","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/ajmg.a.38665","article-title":"Expanding the fetal phenotype: Prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome","volume":"176","author":"Schindewolf","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/ajmg.a.61546","article-title":"Views of adults with 22q11 deletion syndrome on reproductive choices","volume":"182","author":"McNeill","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1365-2788.2012.01639.x","article-title":"Perceived burden and neuropsychiatric morbidities in adults with 22q11.2 deletion syndrome","volume":"58","author":"Karas","year":"2014","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/00125817-200101000-00006","article-title":"Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: Cast a wide FISHing net!","volume":"3","author":"Tonnesen","year":"2001","journal-title":"Genet. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0920-9964(96)00018-7","article-title":"Reproductive fitness in familial schizophrenia","volume":"21","author":"Bassett","year":"1996","journal-title":"Schizophr. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15833","DOI":"10.1038\/ncomms15833","article-title":"Reproductive fitness and genetic risk of psychiatric disorders in the general population","volume":"8","author":"Mullins","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_29","first-page":"347","article-title":"Congenital heart disease in pregnancy","volume":"105","author":"Uebing","year":"2008","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/JPN.0000000000000144","article-title":"Reproductive Health and Women with Congenital Heart Disease: A Practice Update","volume":"30","author":"Osteen","year":"2016","journal-title":"J. Perinat. Neonatal. Nurs."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"687276","DOI":"10.3389\/fped.2021.687276","article-title":"Congenital Heart Diseases Impair Female Fertility","volume":"9","author":"Chien","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"79e1","DOI":"10.1016\/j.ajog.2022.01.002","article-title":"Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome","volume":"227","author":"Dar","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/uog.23699","article-title":"Performance of a targeted cell-free DNA prenatal test for 22q11.2 deletion in a large clinical cohort","volume":"58","author":"Bevilacqua","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2126\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:19:10Z","timestamp":1760145550000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,16]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["genes13112126"],"URL":"https:\/\/doi.org\/10.3390\/genes13112126","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,16]]}}}