ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
This article is part of the Research TopicUnravelling the Genetic and Environmental Factors in Early-Life Development and Future Disease RiskView all 5 articles
Delineating the trajectory of adult chronic diseases and healthcare use for 22q11.2 microdeletion in a general population context
Provisionally accepted
Sarah Malecki1,2,3
Tracy Heung2Samantha Morais4Refik Saskin4Drew Wilton4Therese A Stukel4Eyal Cohen3Amol A. Verma5
Anne S Bassett1,2,6*- 1University of Toronto, Toronto, Canada
- 2Centre for Addiction and Mental Health, Toronto, Canada
- 3SickKids Research Institute, Toronto, Canada
- 4ICES, Toronto, Canada
- 5St Michael's Hospital Li Ka Shing Knowledge Institute, Toronto, Canada
- 6University Health Network, Toronto, Canada
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Summary (280/350 words) Background: Children with complex genetic diseases increasingly survive to adulthood, but adult health is poorly understood. Using a genetics-first approach we investigated the incidence and accrual of cardiovascular and other outcomes in people with molecularly confirmed 22q11.2 microdeletion (22q-cases) compared with general population controls (population-comparators). Methods: Using a retrospective matched cohort study design, we linked 365 adult 22q-cases (median age 32 years; 51% female) to health administrative data for ~15 million individuals with universal healthcare, identifying 3,650 well-matched population-comparators. We used Poisson regression to estimate incidence rate ratios (IRRs) and 95% CI for five cardiovascular/risk conditions and other outcomes, and recurrent event modelling to assess their relative rate (RR) of accrual over a median 28 years of retrospective and prospective health data. Results: Accrual of cardiovascular conditions occurred at a significantly greater relative rate (RR) in 22q-cases than population-comparators (RR 3.8, 95% CI 2.9-4.8; median ages 32, 31), even when restricting to 22q-cases with neither major congenital heart disease (CHD) nor schizophrenia (RR 3.6, 95% CI 2.4-5.4). Incidence was significantly greater in 22q-cases for hypertension and diabetes by age 18-24 (IRR 2.98, 95% CI 1.45-6.14; IRR 3.21, 95% CI 1.42-7.24, respectively), and by age 35-44 for heart failure. Other outcomes also showed increasing trajectories over young adult years in the 22q-case group, e.g., kidney disease, chronic obstructive pulmonary disease, healthcare resource use, and hospitalizations, including for individuals with neither CHD nor schizophrenia. Conclusions: A population-based approach provided new evidence for accumulating illnesses over young adulthood, supporting the need for novel models of anticipatory care for adults with 22q11.2 microdeletion. A similar genetics-first strategy, defining cohorts with shared genetic changes, may facilitate understanding of premature aging mechanisms relevant to the general population.
Keywords: 22q deletion syndrome, accelerated aging, Adult, cardiovascular outcomes, copy number variation, genetic disease, genetics-first, Natural History
Received: 31 Oct 2025; Accepted: 15 Jan 2026.
Copyright: © 2026 Malecki, Heung, Morais, Saskin, Wilton, Stukel, Cohen, Verma and Bassett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Anne S Bassett
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