Cardiac phenotypes in LMNA mutations.

Abstract

Purpose of review: This review highlights the diverse cardiac manifestations of LMNA mutations, focusing on their underlying molecular mechanisms and clinical implications. As LMNA mutations are implicated in cardiomyopathies, such as dilated cardiomyopathy (DCM), arrhythmogenic cardiomyopathy (ARVC), and conduction system diseases, understanding these phenotypes is critical for advancing diagnosis and management strategies.

Recent findings: Recent studies reveal that LMNA mutations disrupt nuclear envelope stability, activating the DNA damage response (DDR) and compromising chromatin organization and mechanotransduction. Mouse models have elucidated pathways linking LMNA dysfunction to fibrosis, arrhythmias, and myocardial remodeling. Emerging evidence demonstrates that fibroblasts play a crucial role in cardiac phenotypes. Advances in genetic screening have also underscored the importance of early identification and risk stratification, particularly for arrhythmias and sudden cardiac death.

Summary: The diverse spectrum of LMNA-related cardiac phenotypes, from isolated conduction defects to severe DCM and ARVC, underscores the necessity of personalized care strategies. Bridging insights from molecular studies and clinical research paves the way for targeted therapies to slow disease progression and improve patient outcomes. Future efforts should prioritize translational research on molecular mechanisms with potential in mouse models, alongside a deeper exploration of genotype-phenotype correlations, to refine and implement effective therapeutic interventions.