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We analyzed cardiology findings in 128 unrelated individuals with distal LCR22 D\u2013H deletions. A total of 62 were newly described and 66 were derived from previous reports. We found that deletions which included LCR22\u2010D 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%\u201346%), which is lower than the prevalence reported for typical, proximal LCR22 A\u2013D deletions (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20093.7E\u22124), especially for conotruncal defects (13\/128, 10.2%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20097.1E\u221213). 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                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098\/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\u201323 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\u201323, particularly within the D\u2013E region including\n                    <jats:italic>MAPK1<\/jats:italic>\n                    and\n                    <jats:italic>HIC2<\/jats:italic>\n                    convey risk for CHD.\n                  <\/jats:p>","DOI":"10.1111\/cge.70118","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T01:41:00Z","timestamp":1765244460000},"page":"859-868","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence and Spectrum of Congenital Heart Disease in Individuals With Distal Chromosome 22q11.22\u201323 Deletions"],"prefix":"10.1111","volume":"109","author":[{"given":"Tanner J.","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Genetics, Pediatrics, Ob\u2010Gyn and Women's Health Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"McGinn","sequence":"additional","affiliation":[{"name":"22q and You Center and Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-5458","authenticated-orcid":false,"given":"T. Blaine","family":"Crowley","sequence":"additional","affiliation":[{"name":"22q and You Center and Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Rockart","sequence":"additional","affiliation":[{"name":"22q and You Center and Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Green","sequence":"additional","affiliation":[{"name":"22q and You Center and Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Giunta","sequence":"additional","affiliation":[{"name":"22q and You Center and Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oanh","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniella","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Genetics, Pediatrics, Ob\u2010Gyn and Women's Health Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0734-5154","authenticated-orcid":false,"given":"Jeroen","family":"Breckpot","sequence":"additional","affiliation":[{"name":"Department of Human Genetics KU Leuven &amp; Center for Human Genetics University Hospitals Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4258-4537","authenticated-orcid":false,"given":"Ann","family":"Swillen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics KU Leuven &amp; Center for Human Genetics University Hospitals Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Cristina","family":"Digilio","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Bambino Ges\u00f9 Hospital  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Unolt","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Bambino Ges\u00f9 Hospital  Rome Italy"},{"name":"Department of Maternal Infantile and Urological Sciences La Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-3769","authenticated-orcid":false,"given":"Carolina","family":"Putotto","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences La Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Pulvirenti","sequence":"additional","affiliation":[{"name":"Department of Maternal Infantile and Urological Sciences La Sapienza 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