Case report: DSP truncation variant p. R1951X leads to arrhythmogenic left ventricular cardiomyopathy

Standardized diagnostic criteria for arrhythmogenic left ventricular cardiomyopathy (ALVC) have been recently proposed. The criteria emphasize structural left ventricle (LV) myocardial change on contrast-enhanced imaging and require the identification of gene variants associated with arrhythmogenic cardiomyopathy.

A 21-year-old man presented for evaluation of exertional syncope and was found to have monomorphic ventricular tachycardia (VT) and an episode of polymorphic VT that degenerated to ventricular fibrillatory cardiac arrest. Documented premature ventricular contractions were of left bundle branch block, inferior axis morphology. Ventricular arrhythmias were successfully suppressed with β-blockade, amiodarone, and lidocaine, and a subcutaneous implantable cardioverter-defibrillator was implanted. Cardiac magnetic resonance imaging demonstrated normal-appearing right ventricle, reduced LV ejection fraction, and sub-epicardial scarring of basal-anterior and anterolateral LV segments. Endomyocardial biopsy showed lymphocytic myocarditis, and genetic testing revealed a pathogenic truncating mutation in the DSP gene, which encodes desmoplakin; this variant was also identified in the patient's mother who carried a diagnosis of non-ischaemic cardiomyopathy. These findings are consistent with a diagnosis of ALVC.

The clinical presentation of ALVC can be very dramatic. The differential for sub-epicardial LV myocardial fibrosis includes myocarditis, sarcoidosis, and in those with a suspicious family history or characteristic electrocardiogram findings, genetic cardiomyopathy. Prompt referral to a genetic counsellor can be lifesaving to patients and their family members.