{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:02:03Z","timestamp":1780286523780,"version":"3.54.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Noonan syndrome (NS) is a rare multisystemic condition among the RASopathy group, characterized by a broad phenotypic spectrum and genetic variability. It results from pathogenic variants in genes regulating the RAS\/MAPK pathway, affecting cell proliferation and differentiation. While the\n                    <jats:italic>PTPN11<\/jats:italic>\n                    gene accounts for approximately 50% of cases, other genes, including\n                    <jats:italic>MRAS<\/jats:italic>\n                    , have been implicated. NS presents with features such as facial dysmorphism, short stature, and cardiac anomalies. Hypertrophic cardiomyopathy (HCM) is a major contributor to mortality, with specific variants conferring higher risk. This article includes a review of the literature on NS with pathogenic\n                    <jats:italic>MRAS<\/jats:italic>\n                    variants and describes an eighth case, the first documented with early and severe antenatal manifestations. The fetus exhibited increased nuchal translucency, agenesis of the ductus venosus, pulmonary lymphangiectasia, and complex hepatic vascular anomalies. A cesarean section was performed at 33\u00a0weeks' gestation due to worsening fetal pleural effusions and maternal intolerance to polyhydramnios. Despite intensive postnatal care, the newborn died from refractory shock and multi\u2010organ failure. Histopathology revealed HCM, obliterative portal venopathy and lymphangiectasia, consistent with NS pathology. These findings suggest that pathogenic\n                    <jats:italic>MRAS<\/jats:italic>\n                    variants confer a high risk of severe HCM (100% of cases). Moreover, emerging targeted therapies, such as MEK inhibitors, offer potential for treatment.\n                  <\/jats:p>","DOI":"10.1002\/pd.70134","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T02:56:14Z","timestamp":1774234574000},"page":"581-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypertrophic Cardiomyopathy as a Key Feature of MRAS\u2010Related Noonan Syndrome: New Case and Comprehensive Literature Review"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5054-0041","authenticated-orcid":false,"given":"Romain","family":"Martineau","sequence":"first","affiliation":[{"name":"Resident in Gynecology Obstetrics and Fetopathology Montpellier University  Montpellier France"},{"name":"Medical Genetics Department University Hospital of Montpellier Montpellier University  Montpellier France"},{"name":"Department of Obstetrics and Gynecology University Hospital of Montpellier Montpellier University  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance","family":"Wells","sequence":"additional","affiliation":[{"name":"Medical Genetics Department University Hospital of Montpellier Montpellier University  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Hospital of Montpellier Montpellier University  Montpellier France"},{"name":"Inserm CESP Center for Research in Epidemiology and Population Health Reproduction and Child Development  Villejuif France"},{"name":"DESBREST Institute of Epidemiology and Public Health (IDESP) University of Montpellier INSERM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-1089","authenticated-orcid":false,"given":"Sophie","family":"Collardeau\u2010Frachon","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospices Civils de Lyon &amp; Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-1706","authenticated-orcid":false,"given":"Valentin","family":"Ruault","sequence":"additional","affiliation":[{"name":"Medical Genetics Department University Hospital of Montpellier Montpellier University  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6948-120X","authenticated-orcid":false,"given":"Sophie","family":"Colomb","sequence":"additional","affiliation":[{"name":"Montpellier Criminal Law and Forensic Sciences Team (EDPFM) University of Montpellier  Montpellier France"},{"name":"Department of Forensic Medicine Emergency Department Montpellier University Hospital Center  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Michel","family":"Faure","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Hospital of Montpellier Montpellier University  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Bartholmot","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Hospital of Montpellier Montpellier University  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Vincenti","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Congenital Cardiology M3C Regional Reference Centre Montpellier University Hospital  Montpellier France"},{"name":"PhyMedExp INSERM CNRS University of Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Ganne","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Cytogenomics Department University Hospital of Montpellier Montpellier University  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-0935","authenticated-orcid":false,"given":"Marjolaine","family":"Willems","sequence":"additional","affiliation":[{"name":"Medical Genetics Department University Hospital of Montpellier Montpellier University  Montpellier France"},{"name":"Institute for Neurosciences of Montpellier University Montpellier INSERM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"M.Le DrefandHaute Autorit\u00e9 de Sant\u00e9 (HAS) \u201cProtocole National de Diagnostic et de Soins (PNDS)\u201d (2021)."},{"key":"e_1_2_12_3_1","unstructured":"Orphanet.Syndrome de Noonan https:\/\/www.orpha.net\/fr\/disease\/detail\/648."},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000276766"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.114"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.249"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13195735"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6133"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild\u20102021\u2010322858"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13533"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91225"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz108"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61261"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62376"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.32034"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annpat.2025.04.007"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.046300"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.65"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.119.002648"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.01.066"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.01.105"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)31373-0"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000\u2010017\u20100647\u2010y"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.70134","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pd.70134","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.70134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T03:46:50Z","timestamp":1780285610000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.70134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,22]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/pd.70134"],"URL":"https:\/\/doi.org\/10.1002\/pd.70134","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,22]]},"assertion":[{"value":"2025-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}