When The “Genes” No Longer Fit: An Unusual Presentation of LMNA-related Cardiomyopathy

Introduction The diagnosis of dilated cardiomyopathy from genetic mutation of Lamin A/C (LMNA) is quite challenging in absence of known family disease or signs of skeletal myopathy. We present a case of high-grade AV block and septal ventricular tachycardia (VT) requiring orthotopic heart transplantation with post-transplant genetic testing showing LMNA-related dilated cardiomyopathy. Case A 58-year-old man with history of orthotopic liver transplant (OLT) for Hepatitis C cirrhosis and no familial cardiac history initially presented with symptomatic, sustained left bundle left superior axis ventricular tachycardia at 230 bpm. Baseline ECG after DCCV demonstrated a LBBB with periods of 2:1 AV block. Patient underwent an ischemic evaluation which was unremarkable. Cardiac MRI was negative for infiltrative disease but did show midmyocardial late gadolinium enhancement at the inferoseptal and apical right ventricle. He underwent secondary prevention CRT-D implantation. He had recurrent VT requiring radiofrequency ablation for inducible bundle-branch reentry VT. One year later, he presented with recurrent VT and underwent attempted radiofrequency ablation of numerous septal VT morphologies resulting in shock-refractory sustained VT complicated by cardiogenic shock requiring VA-ECMO and ultimately orthotopic heart transplantation. Pathology of the explanted heart showed scarring and fatty infiltration of the RV septum and free wall suggestive of a variant of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, despite suspicion for ARVC on pathology, genetic testing showed a genetic mutation in Lamin A/C Gene, suggestive of laminopathy. Conclusion Our case shows that LMNA-related dilated cardiomyopathy can present with phenotypic appearance similar to patients with pathologic suspicion of ARVC. Although LMNA-related dilated cardiomyopathy contributes to 6-8% of familial related cardiomyopathy, it is often difficult to diagnose due to its inheritance and penetrance. Patients presenting with unclear etiology of dilated cardiomyopathy and malignant ventricular arrhythmias should prompt a suspicion for LMNA-related cardiomyopathy.