{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:50Z","timestamp":1791041930638,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome (NS) has been associated with an increased risk of lymphatic anomalies, with an estimated prevalence of 20%. The prevalence of lymphatic anomalies seems to differ between pathogenic variants. Therefore, this study aims to describe the clinical presentation, prevalence and genotype\u2013phenotype correlations of lymphatic anomalies during life in patients with NS. This retrospective cohort study included patients (<jats:italic>n<\/jats:italic>\u00a0=\u2009115) who were clinically and genetically diagnosed with NS and visited the Noonan expertise Center of the Radboud University Medical Center between January 2015 and March 2021. Data on lymphatic anomalies during lifetime were obtained from medical records. Lymphatic anomalies most often presented as an increased nuchal translucency, chylothorax and\/or lymphedema. Prenatal lymphatic anomalies increased the risk of lymphatic anomalies during infancy (OR 4.9, 95% CI 1.7\u201314.6). The lifetime prevalence of lymphatic anomalies was 37%. Genotype\u2013phenotype correlations showed an especially high prevalence of lymphatic anomalies during infancy and childhood in patients with a pathogenic <jats:italic>SOS2<\/jats:italic> variant (<jats:italic>p<\/jats:italic>\u00a0=\u20090.03 and <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.01, respectively). This study shows that patients with NS have a high predisposition for developing lymphatic anomalies during life. Especially patients with prenatal lymphatic anomalies have an increased risk of lymphatic anomalies during infancy. Genotype\u2013phenotype correlations were found in pathogenic variants in <jats:italic>SOS2<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/ajmg.a.62955","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T07:37:15Z","timestamp":1660808235000},"page":"3242-3261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-5782","authenticated-orcid":false,"given":"Jessie W.","family":"Swarts","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Amalia Children's Hospital, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0553-7064","authenticated-orcid":false,"given":"Lotte E. 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