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Gain\u2010of\u2010function missense heterozygous variants affecting the Ile500 residue and Arg496 residue of the\n                    <jats:italic>SMAD4<\/jats:italic>\n                    gene are implicated in this condition. In this article, we aim to understand the spectrum of congenital anomalies in Myhre syndrome by studying a cohort of previously unreported patients alongside published literature. Our analysis revealed that the musculoskeletal system was the most common system to be affected, followed by the cardiovascular system. Intrauterine growth restriction was the most reported intrauterine anomaly. Although there was no clear genotype\u2013phenotype correlation, it appears that the Ile500Thr variant showed early multisystem involvement compared to other variants.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.c.70007","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:00:29Z","timestamp":1776063629000},"page":"392-404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spectrum of Congenital Anomalies in Myhre Syndrome\u2014Insights Into Effects Brought by Altered\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2 Signaling via Gain\u2010of\u2010Function Variants in\n                    <scp>\n                      <i>SMAD4<\/i>\n                    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