{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T19:45:07Z","timestamp":1778010307266,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"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 deletion syndrome (22q11.2DS) manifests as a wide range of medical conditions across a number of systems. Pediatric growth deficiency with some catch-up growth is reported, but there are few studies of final adult height. We aimed to investigate how final adult height in 22q11.2DS compared with general population norms, and to examine predictors of short stature in in a cohort of 397 adults with 22q11.2DS (aged 17.6\u201376.3 years) with confirmed typical 22q11.2 microdeletion (overlapping the LCR22A to LCR22B region). We defined short stature as &lt;3rd percentile using population norms. For the subset (n = 314, 79.1%) with 22q11.2 deletion extent, we used a binomial logistic regression model to predict short stature in 22q11.2DS, accounting for effects of sex, age, ancestry, major congenital heart disease (CHD), moderate-to-severe intellectual disability (ID), and 22q11.2 deletion extent. Adult height in 22q11.2DS showed a normal distribution but with a shift to the left, compared with population norms. Those with short stature represented 22.7% of the 22q11.2DS sample, 7.6-fold greater than population expectations (p &lt; 0.0001). In the regression model, moderate-to-severe ID, major CHD, and the common LCR22A-LCR22D (A-D) deletion were significant independent risk factors for short stature while accounting for other factors (model p = 0.0004). The results suggest that the 22q11.2 microdeletion has a significant effect on final adult height distribution, and on short stature with effects appearing to arise from reduced gene dosage involving both the proximal and distal sub-regions of the A-D region. Future studies involving larger sample sizes with proximal nested 22q11.2 deletions, longitudinal lifetime data, parental heights, and genotype data will be valuable.<\/jats:p>","DOI":"10.3390\/genes13112038","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:56:36Z","timestamp":1667908596000},"page":"2038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Adult Height, 22q11.2 Deletion Extent, and Short Stature in 22q11.2 Deletion Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Tracy","family":"Heung","sequence":"first","affiliation":[{"name":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"},{"name":"The Dalglish Family 22q Clinic, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigid","family":"Conroy","sequence":"additional","affiliation":[{"name":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"},{"name":"Undergraduate Medical Education, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Malecki","sequence":"additional","affiliation":[{"name":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, ON M5S 1A4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Ha","sequence":"additional","affiliation":[{"name":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"},{"name":"The Dalglish Family 22q Clinic, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-1539","authenticated-orcid":false,"given":"Erik","family":"Boot","sequence":"additional","affiliation":[{"name":"The Dalglish Family 22q Clinic, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Advisium, \u2019s Heeren Loo, 3818 LA Amersfoort, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Corral","sequence":"additional","affiliation":[{"name":"The Dalglish Family 22q Clinic, 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":"Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5S 2S1, Canada"},{"name":"The Dalglish Family 22q Clinic, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A4, Canada"},{"name":"Toronto General Hospital Research Institute, Toronto, ON M5G 2C4, Canada"},{"name":"Campbell Family Mental Health Research Institute, Toronto, ON M5G 2C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jpeds.2011.02.039","article-title":"Practical guidelines for managing patients with 22q11.2 deletion syndrome","volume":"159","author":"Bassett","year":"2011","journal-title":"J. Pediatr."},{"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","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_4","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1002\/ajmg.a.35426","article-title":"Syndrome-specific growth charts for 22q11.2 deletion syndrome in Caucasian children","volume":"158","author":"Habel","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/00125817-200101000-00007","article-title":"Auxological evaluation in patients with DiGeorge\/velocardiofacial syndrome (deletion 22q11.2 syndrome)","volume":"3","author":"Digilio","year":"2001","journal-title":"Genet. Med."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.ajhg.2011.10.014","article-title":"Genome-wide association of copy-number variation reveals an association between short stature and the presence of low-frequency genomic deletions","volume":"89","author":"Dauber","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/ejhg.2013.203","article-title":"Copy number variants in patients with short stature","volume":"22","author":"Lui","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zahnleiter, D., Uebe, S., Ekici, A.B., Hoyer, J., Wiesener, A., Wieczorek, D., Kunstmann, E., Reis, A., Doerr, H.G., and Rauch, A. (2013). Rare copy number variants are a common cause of short stature. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003365"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/s41467-017-00556-x","article-title":"CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits","volume":"8","author":"Tuke","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Owen, D., Bracher-Smith, M., Kendall, K.M., Rees, E., Einon, M., Escott-Price, V., Owen, M.J., O\u2019Donovan, M.C., and Kirov, G. (2018). Effects of pathogenic CNVs on physical traits in participants of the UK Biobank. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5292-7"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1530\/EJE-21-1104","article-title":"Hypertriglyceridemia in young adults with a 22q11.2 microdeletion","volume":"187","author":"Blagojevic","year":"2022","journal-title":"Eur. J. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Harris, M.A., Brett, C.E., Deary, I.J., and Starr, J.M. (2016). Associations among height, body mass index and intelligence from age 11 to age 78 years. BMC Geriatr., 16.","DOI":"10.1186\/s12877-016-0340-0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.2307\/27784427","article-title":"The role of height in the sex difference in intelligence","volume":"122","author":"Kanazawa","year":"2009","journal-title":"Am. J. Psychol."},{"key":"ref_15","first-page":"e211","article-title":"Short stature among children undergoing cardiac surgery for congenital heart defects","volume":"117","author":"Larios","year":"2019","journal-title":"Arch. Argent. Pediatr."},{"key":"ref_16","first-page":"241","article-title":"Evolution of weight and height of children with congenital heart disease undergoing surgical treatment","volume":"29","author":"Peres","year":"2014","journal-title":"Rev. Bras. Cir. Cardiovasc."},{"key":"ref_17","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_18","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_19","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_20","unstructured":"Rani, D., Shrestha, R., Kanchan, T., and Krishan, K. (2022). Short Stature, StatPearls."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.2307\/1130466","article-title":"Longitudinal correlation analysis of standing height and intelligence","volume":"56","author":"Humphreys","year":"1985","journal-title":"Child. Dev."},{"key":"ref_23","first-page":"313","article-title":"Biological factors and psychometric intelligence: A review","volume":"117","author":"Johnson","year":"1991","journal-title":"Genet. Soc. Gen. Psychol. Monogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/nature09410","article-title":"Hundreds of variants clustered in genomic loci and biological pathways affect human height","volume":"467","author":"Estrada","year":"2010","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature21039","article-title":"Rare and low-frequency coding variants alter human adult height","volume":"542","author":"Marouli","year":"2017","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1002\/ajmg.a.40359","article-title":"Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects","volume":"176","author":"Zhao","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/s41436-020-01046-0","article-title":"Focused Revision: ACMG practice resource: Genetic evaluation of short stature","volume":"23","author":"Mintz","year":"2021","journal-title":"Genet. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fiksinski, A.M., Heung, T., Corral, M., Breetvelt, E.J., Costain, G., Marshall, C.R., Kahn, R.S., Vorstman, J.A.S., and Bassett, A.S. (2021). Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model. Psychol. Med., 1\u20139.","DOI":"10.1017\/S0033291720005279"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"669441","DOI":"10.3389\/fgene.2021.669441","article-title":"Polygenic Scores and Parental Predictors: An Adult Height Study Based on the United Kingdom Biobank and the Framingham Heart Study","volume":"12","author":"You","year":"2021","journal-title":"Front. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13229-020-00407-5","article-title":"Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank","volume":"12","author":"Yap","year":"2021","journal-title":"Mol. Autism."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41586-022-05275-y","article-title":"A saturated map of common genetic variants associated with human height","volume":"610","author":"Yengo","year":"2022","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4496","DOI":"10.1038\/s41380-020-0654-3","article-title":"Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion","volume":"26","author":"Cleynen","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s11689-015-9113-x","article-title":"Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms","volume":"7","author":"Guna","year":"2015","journal-title":"J. Neurodev. Disord."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2038\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:11:04Z","timestamp":1760145064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,5]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["genes13112038"],"URL":"https:\/\/doi.org\/10.3390\/genes13112038","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,5]]}}}