| Title: |
Hypertrophic Cardiomyopathy as a Key Feature of MRAS‐Related Noonan Syndrome: New Case and Comprehensive Literature Review |
| Authors: |
Martineau, Romain; Wells, Constance; Fuchs, Florent; Collardeau-Frachon, Sophie; Ruault, Valentin; Colomb, Sophie; Faure, Jean‐michel; Bartholmot, Caroline; Vincenti, Marie; Ganne, Benjamin; Willems, Marjolaine |
| Contributors: |
CHU Montpellier = Montpellier University Hospital; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Université de Montpellier (UM); Institut Desbrest d'Epidémiologie et de Santé Publique (IDESP); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); Centre de recherche en épidémiologie et santé des populations (CESP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse; AP-HP. Université Paris Saclay-AP-HP. Université Paris Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Hospices Civils de Lyon (HCL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon; Equipe de Droit Pénal et de sciences Forensiques de Montpellier (EDPFM); Physiologie & médecine expérimentale du Cœur et des Muscles U 1046 (PhyMedExp); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Institut des Neurosciences de Montpellier (INM) |
| Source: |
ISSN: 0197-3851. |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2026 |
| Subject Terms: |
MRAS; RASopathies; fetal pathology; hypertrophic cardiomyopathy; noonan syndrome; prenatal; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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 PTPN11 gene accounts for approximately 50% of cases, other genes, including MRAS , 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 MRAS 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 weeks' gestation due to worsening fetal pleural effusions and maternal intolerance to polyhydramnios. Despite intensive postnatal care, the newborn died from refractory shock and multi‐organ failure. Histopathology revealed HCM, obliterative portal venopathy and lymphangiectasia, consistent with NS pathology. These findings suggest that pathogenic MRAS variants confer a high risk of severe HCM (100% of cases). Moreover, emerging targeted therapies, such as MEK inhibitors, offer potential for treatment. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41866303; PUBMED: 41866303 |
| DOI: |
10.1002/pd.70134 |
| Availability: |
https://hal.science/hal-05562494; https://hal.science/hal-05562494v1/document; https://hal.science/hal-05562494v1/file/2026%20Martineau%20et%20al.,%20Hypertrophic%20Cardiomyopath.pdf; https://doi.org/10.1002/pd.70134 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.261B84C3 |
| Database: |
BASE |