Work

Hypertrophic Cardiomyopathy as a Key Feature of MRAS‐Related Noonan Syndrome: New Case and Comprehensive Literature Review

Year: 2026

Type: article

Abstract: 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.

Source: Prenatal Diagnosis

DOI: 10.1002/pd.70134