Extensive cardiac involvement in laminopathies diagnosed in pediatric-aged patients: A single-center study.

Background: Pathogenic variations in lamin A/C (LMNA) result in a group of inherited conditions termed laminopathies. Cardiac manifestations of laminopathies include atrial and ventricular arrhythmias, atrioventricular conduction disorders, and cardiomyopathy, with or without skeletal muscle involvement. Because of rarity and previous cardiac characterization as adult onset, pediatric data are limited.

Objective: This study sought to investigate the natural history of cardiac disease in pediatric patients with pathogenic LMNA variants.

Methods: We identified patients ≤18 years with genetically confirmed pathogenic variants in LMNA observed at a single center between 2003 and 2024. Clinical phenotypes along with cardiac test results were retrospectively catalogued.

Results: We identified 12 patients with pathogenic LMNA variant with a median age of 4.9 years at diagnosis (interquartile range, 3.7-10.7 years). Of the 12 patients, 9 (75%) were male and 10 (83%) had skeletal muscle involvement. Cardiac manifestations developed in 9 patients (75%) during a median follow-up of 9.5 years (interquartile range, 7.0-13.3 years). Nine patients (75%) had conduction abnormalities or arrhythmias (atrioventricular block, ventricular/atrial tachycardias), and 4 (33%) had cardiovascular implantable electronic devices placed. Two (17%) patients were diagnosed with cardiomyopathy, 1 (8%) requiring heart transplant. Two (17%) patients died during the study.

Conclusions: Cardiac involvement, specifically cardiomyopathy and progressive conduction system abnormalities, were common in pediatric patients with pathogenic LMNA variants. Early genetic diagnosis of laminopathies with frequent surveillance for arrhythmias and cardiac dysfunction is necessary for more timely initiation of advanced therapies to prevent adverse events. More comprehensive phenotype-genotype correlation is strongly needed to better understand early cardiac manifestations in laminopathies.