Medicine (Baltimore). 2026 Jan 9;105(2):e46340. doi: 10.1097/MD.0000000000046340.
ABSTRACT
RATIONALE: Noonan syndrome (NS) is a RASopathy most frequently associated with mutations in HRAS, NRAS, KRAS, and RRAS2. The contribution of MRAS variants to NS pathogenesis remains poorly characterized, and infective endocarditis (IE) is extremely rare in patients with NS.
PATIENT CONCERNS: A 22-year-old woman presented with typical dysmorphic features of NS, including short stature, broad forehead, hypertelorism, low-set posteriorly rotated ears, and a broad neck. She developed fever and progressive exertional dyspnea.
DIAGNOSES: Echocardiography demonstrated obstructive hypertrophic cardiomyopathy with vegetation located in the left ventricular outflow tract. Blood cultures grew Streptococcus mutans. Whole-exome sequencing identified a heterozygous MRAS c.203C>T (p.Thr68Ile) mutation affecting a highly conserved residue among RASopathy-associated GTPases, supporting the diagnosis of MRAS-associated Noonan syndrome complicated by infective endocarditis.
INTERVENTIONS: Antibiotic therapy was escalated to intravenous gentamicin (60 mg daily) combined with ceftriaxone in accordance with the 2023 European Society of Cardiology guidelines for infective endocarditis.
OUTCOMES: After one month of intravenous gentamicin and ceftriaxone therapy, fever resolved, and follow-up echocardiography showed disappearance of the vegetation. Residual cardiac abnormalities persisted, including marked left ventricular hypertrophy with left ventricular outflow tract obstruction, left atrial enlargement, moderate mitral regurgitation, patent foramen ovale with minor shunting, and impaired diastolic function. Exertional dyspnea remained despite resolution of the infection.
LESSONS: This case expands the genotypic spectrum of Noonan syndrome by supporting MRAS mutations as pathogenic drivers. It also identifies infective endocarditis as a previously unreported complication in MRAS-associated NS with outflow tract obstruction, highlighting the importance of careful cardiac surveillance in patients with RASopathies.
PMID:41517739 | DOI:10.1097/MD.0000000000046340