Noonan syndrome (NS) is a Mendelian phenotype, member of a group of disorders sharing neurocardiofaciocutaneous involvement, known as RASopathies, caused by germline variants in genes coding for components of the RAS/MAPK signaling pathway. Recently, a novel gene of the RAS family (MRAS) was reported to be associated with NS in five children, all of them presenting, among the cardinal features of NS, the same cardiac finding, hypertrophic cardiomyopathy (HCM). We report on a 2-month-old infant boy also presenting this cardiac anomaly that evolved to a fatal outcome after a surgical myectomy. In addition, a thick walled left ventricle apical aneurysm, rarely described in NS, was also disclosed. Next-generation sequencing revealed a missense, previously reported variant in MRAS (p.Thr68Ile). This report reinforces the high frequency of HCM among individuals harboring MRAS variants, contrasting to the 20% overall prevalence of this cardiac anomaly in NS. Thus, these preliminary data suggest that variants in MRAS per se are high risk factors for the development of an early, severe HCM, mostly of them with left ventricle outflow tract obstruction, with poor prognosis. Because of the severity of the cardiac involvement, other clinical findings could not be addressed in detail. Therefore, long-term follow-up of these individuals and further descriptions are required to fully understand the complete phenotypic spectrum of NS associated with MRAS germline variants, including if these individuals present an increased risk for cancer.
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http://dx.doi.org/10.1002/ajmg.a.62376 | DOI Listing |
J Cardiol
January 2025
Department of Cardiology, St. Luke's University Health Network, Bethlehem, PA, USA. Electronic address:
Background: Hypertrophic cardiomyopathy (HCM) is a common genetic disease with estimated prevalence of 0.2-0.5 %.
View Article and Find Full Text PDFBackground: Disopyramide is used to treat heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM) with known medium-term efficacy and safety, while long-term outcomes are unknown.
Methods And Results: A total of 92 consecutive patients with symptomatic obstructive HCM with peak left ventricular outflow tract gradients of ≥30 mm Hg at rest or with provocation who were maintained on disopyramide for ≥5 years at 2 dedicated HCM centers were included: 92 patients; mean age, 62.5 years; 54% women; treated with disopyramide for median 7.
Mol Genet Genomic Med
January 2025
Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Background: Sengers syndrome is an autosomal recessive mitochondrial DNA depletion syndrome characterized by hypertrophic cardiomyopathy, congenital cataracts, skeletal myopathy, exercise intolerance, and lactic acidosis. Dysfunction of acylglycerol kinase (AGK) is responsible for the disease, and several AGK gene variants have been reported.
Methods: We employed a comprehensive genomic analysis approach, including whole-genome sequencing and RNA sequencing, combined with various bioinformatics tools.
Circ Cardiovasc Qual Outcomes
January 2025
Division of Cardiovascular Medicine, Department of Internal Medicine, Lahey Hospital and Medical Center, Burlington, MA (S.S.D.).
JACC Adv
December 2024
Department of Medicine, The Cardiac Clinic, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
Background: Cardiomyopathies are an important cause of heart failure in Africa yet there are limited data on etiology and clinical phenotypes.
Objectives: The IMHOTEP (African Cardiomyopathy and Myocarditis Registry Program) was designed to systematically collect data on individuals diagnosed with cardiomyopathy living in Africa.
Methods: In this multicenter pilot study, patients (age ≥13 years) were eligible for inclusion if they had a diagnosis of cardiomyopathy or myocarditis.
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