{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:45:08Z","timestamp":1774266308713,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The antenatal phenotypic spectrum of Noonan Syndrome (NS) requires better characterization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter retrospective observational included 16 fetuses with molecularly confirmed NS admitted for fetopathological examination between 2009 and 2016.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 12 pathogenic variants (PV) in <jats:italic>PTPN11<\/jats:italic> (80%), 5 (42%) fell between position c.179 and c.182. Ultrasound showed increased nuchal translucency (<jats:italic>n<\/jats:italic>\u00a0=\u00a013\/16, 93%), increased nuchal fold after 15\u00a0weeks of gestation (<jats:italic>n<\/jats:italic>\u00a0=\u00a012\/16, 75%), pleural effusions (<jats:italic>n<\/jats:italic>\u00a0=\u00a011\/16, 69%), polyhydramnios (<jats:italic>n<\/jats:italic>\u00a0=\u00a09\/16, 56%), hydrops (<jats:italic>n<\/jats:italic>\u00a0=\u00a07\/16, 44%), cardiovascular (<jats:italic>n<\/jats:italic>\u00a0=\u00a06\/16, 38%) and cerebral (<jats:italic>n<\/jats:italic>\u00a0=\u00a04\/16, 25%) anomalies. Fetopathological examination found dysmorphic features in all cases, cardiovascular anomalies (<jats:italic>n<\/jats:italic>\u00a0=\u00a012\/15, 80%), pulmonary hypoplasia (<jats:italic>n<\/jats:italic>\u00a0=\u00a010\/15, 67%), effusions (<jats:italic>n<\/jats:italic>\u00a0=\u00a07\/15, 47%) and neuropathological anomalies (<jats:italic>n<\/jats:italic>\u00a0=\u00a05\/15, 33%). Hydrops was significantly (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.02) more frequent in the four fetuses with <jats:italic>RIT1<\/jats:italic>, <jats:italic>NRAS<\/jats:italic> and <jats:italic>RAF1<\/jats:italic> PV versus the 12 fetuses with <jats:italic>PTPN11<\/jats:italic> PV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Increased nuchal translucency and nuchal fold is common in NS. Noonan Syndrome antenatal phenotype showed high in utero fetal death, hydrops, prenatal pleural effusion and pulmonary hypoplasia, although the inclusion of only deceased fetuses will have selected more severe phenotypes. Non\u2010specific cardiovascular and neurological abnormalities should be added to NS antenatal phenotype. Next generation sequencing will help detect more genotypes, clarifying the prenatal phenotype and identifying genotype\u2010phenotype correlations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6133","type":"journal-article","created":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T16:34:10Z","timestamp":1647102850000},"page":"574-582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Extending the prenatal Noonan's phenotype by review of ultrasound and autopsy data"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-9581","authenticated-orcid":false,"given":"Audrey","family":"Lamouroux","sequence":"first","affiliation":[{"name":"Clinical Genetics Department Montpellier University Hospital University of Montpellier  Montpellier France"},{"name":"Obstetrical Gynecology Department N\u00eemes University Hospital University of Montpellier  N\u00eemes France"},{"name":"Charles 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