Prevalence and Spectrum of Congenital Heart Disease in Individuals With Distal Chromosome 22q11.22–23 Deletions

This study is aimed at determining the spectrum of congenital heart disease associated with distal 22q11.22-23 deletions flanked by low copy repeats, LCR22 D-H. We analyzed cardiology findings in 128 unrelated individuals with distal LCR22 D-H deletions. A total of 62 were newly described and 66 were derived from previous reports. We found that deletions which included LCR22-D as the proximal endpoint were the most prevalent in the cohort (104/128, 81.3%). Clinically relevant congenital heart disease was identified in 48 individuals (37.5%, 95% CI 29%-46%), which is lower than the prevalence reported for typical, proximal LCR22 A-D deletions (p = 3.7E-4), especially for conotruncal defects (13/128, 10.2%; p = 7.1E-13). Mild to moderate CHD predominated, including ventricular septal defects (22/128), bicuspid aortic valve (9/128) and mild cardiomyopathy (3/128). Persistent truncus arteriosus was the most prevalent (n = 8/13) conotruncal heart defect, but other anomalies also occurred in singleton cases. These findings support the need for cardiac evaluation in all individuals with distal 22q11.22-23 deletions, increased use of clinical genetic testing in syndromic individuals with these findings, and molecular studies in model systems. The results demonstrate that reduced gene dosage of distal 22q11.21-23, particularly within the D-E region including MAPK1 and HIC2 convey risk for CHD.

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Publication Details

Journal
Clinical Genetics
Published
2025-12-08
DOI
https://doi.org/10.1111/cge.70118
Primary Topic
Congenital heart defects research
Type
article
Field-Weighted Citation Impact
0.00

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article

Prevalence and Spectrum of Congenital Heart Disease in Individuals With Distal Chromosome 22q11.22–23 Deletions

Oanh Tran, Bruno Marino, M. Cristina Digilio, Elaine H. Zackai et al.
Clinical Genetics
Congenital heart defects research
article

Prevalence and Spectrum of Congenital Heart Disease in Individuals With Distal Chromosome 22q11.22–23 Deletions

Oanh Tran, Bruno Marino, M. Cristina Digilio, Elaine H. Zackai, Marta Unolt, Audrey Green, Jeroen Breckpot, Thomas A. Nelson, Beverly S. Emanuel, Elizabeth Goldmuntz, Bernice E. Morrow, Federica Pulvirenti, Donna M. McDonald‐McGinn, Daniella Miller, Erik Boot, Carolina Putotto, Daniel E. McGinn, Zhengdong D. Zhang, Terrence Blaine Crowley, Ann Swillen, Victoria Giunta, Anne S. Bassett, Lydia Rockart
article en

Abstract

This study is aimed at determining the spectrum of congenital heart disease associated with distal 22q11.22-23 deletions flanked by low copy repeats, LCR22 D-H. We analyzed cardiology findings in 128 unrelated individuals with distal LCR22 D-H deletions. A total of 62 were newly described and 66 were derived from previous reports. We found that deletions which included LCR22-D as the proximal endpoint were the most prevalent in the cohort (104/128, 81.3%). Clinically relevant congenital heart disease was identified in 48 individuals (37.5%, 95% CI 29%-46%), which is lower than the prevalence reported for typical, proximal LCR22 A-D deletions (p = 3.7E-4), especially for conotruncal defects (13/128, 10.2%; p = 7.1E-13). Mild to moderate CHD predominated, including ventricular septal defects (22/128), bicuspid aortic valve (9/128) and mild cardiomyopathy (3/128). Persistent truncus arteriosus was the most prevalent (n = 8/13) conotruncal heart defect, but other anomalies also occurred in singleton cases. These findings support the need for cardiac evaluation in all individuals with distal 22q11.22-23 deletions, increased use of clinical genetic testing in syndromic individuals with these findings, and molecular studies in model systems. The results demonstrate that reduced gene dosage of distal 22q11.21-23, particularly within the D-E region including MAPK1 and HIC2 convey risk for CHD.

Clinical Genetics
Albert Einstein College of Medicine (US), University Health Network (CA), Children's Hospital of Philadelphia (US), Centre for Addiction and Mental Health (CA), University of Toronto (CA), Toronto General Hospital (CA), Maastricht University (NL), Center for Human Genetics (US), Bambino Gesù Children's Hospital (IT), 's Heeren Loo (NL), University of Pennsylvania (US), Sapienza University of Rome (IT)
Children's Hospital of Philadelphia, University of Toronto, Sapienza Università di Roma, National Institutes of Health, Canadian Institutes of Health Research
Openalex Percentile: Top 64%
Congenital heart defects research
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