Abstract 4361068: Hypertrophic Cardiomyopathy in a Patient With <i>BAG3</i> -Associated Charcot-Marie-Tooth Disease: A Rare Cardiac Manifestation

Abstract

Introduction: BAG3 pathogenic variants and Charcot-Marie-Tooth (CMT) have been linked with various cardiac conditions, but rarely hypertrophic cardiomyopathy (HCM). This case shows a unique presentation of BAG3 pathogenic variants, including CMT and HCM and highlights the importance of cardiac evaluation for BAG3 -related CMT. Description of Case: A 44-year-old female with CMT was referred to the department of genetics due to a family history of CMT. Genetic testing revealed a pathogenic variant in BAG3 , specified c. 1408C&gt;T ; this result prompted a referral to cardiogenomics clinic. During her cardiac evaluation, she reported a year-long history of palpitations, fatigue, orthopnea, and near-syncope. Echocardiography showed a left ventricular outflow tract (LVOT) gradient of 42 mmHg with Valsalva and asymmetric hypertrophy of the mid to apical left ventricular cavity. Cardiac MRI confirmed asymmetric HCM with thickening of the basal and mid interventricular septum and anterior segments of the myocardial wall, up to 19 mm, and mild LVOT flow acceleration. She was initiated on a cardiac myosin inhibitor for obstructive HCM, and after one year, her LVOT gradient decreased to 13 mmHg. At 1-year follow-up, she was feeling well with rare palpitations and fatigue. Discussion: The BAG3 gene encodes Bcl-2-associated athanogene 3 (BAG3), involved in sarcomere maintenance, apoptosis regulation, and mitochondrial function. While BAG3 -related cardiomyopathy is typically dilated in phenotype, other conditions, such as left ventricular noncompaction and peripartum cardiomyopathy, have been described. HCM is rare, with limited associations to specific BAG3 variants, such as C151R; this is distinct from the c. 1408C&gt;T variant mentioned above. BAG3 mutations may also lead to adult-onset CMT, often with associated cardiac findings, including arrythmias and conduction abnormalities. However, to our knowledge, HCM in the context of BAG3 -associated CMT has not been previously reported. This case expands the known cardiac phenotype of BAG3 -related disease and underscores the importance of cardiovascular evaluation in patients with neuromuscular manifestations of BAG3 variants.