Abstract 14956: Extensive Cardiac Involvement in Laminopathies Diagnosed in Pediatric-Aged Patients: A Single Center Study

Abstract

Introduction: Lamin A/C ( LMNA ) gene mutations result in a heterogeneous 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 this disease is rare and typically presents in adulthood, pediatric data is limited. Methods: We identified patients < 18 years with genetically confirmed mutations in LMNA followed at our center between 2003 and 2021. Clinical phenotypes along with cardiac test results were retrospectively catalogued. Results: We identified 12 patients with a median age of 5 years at diagnosis (IQR 4-11 years) with a LMNA mutation. Nine (75%) patients were male and 10 (83%) had associated skeletal muscle involvement. Of the 12 patients, 10 (83%) developed cardiac manifestations over a median follow up period of 111 months (IQR 91-116 months). Seven patients (58%) had documented arrhythmias (AV block, ventricular/atrial tachycardias) and 3 (25%) underwent pacemaker and/or implantable cardiac defibrillator placement. Three (25%) patients were diagnosed with cardiomyopathy with 1 (8%) requiring a ventricular assist device and 1 (8%) requiring continuous intravenous inotropes and subsequent transplant. Three (25%) patients died during the study period, one awaiting transplant, one from complications post-transplant, and one from non-cardiac causes. Conclusions: Cardiac involvement, specifically cardiomyopathy and progressive conduction system abnormalities, were common in pediatric patients with LMNA mutations. Early genetic diagnosis of laminopathies followed by frequent surveillance for dysrhythmia and dysfunction is necessary for more timely initiation of advanced cardiac therapies to prevent adverse events. More comprehensive phenotype-genotype correlation is strongly needed.