Heterozygous desmoplakin (DSP) variants presenting with early onset cardiomyopathy and refractory ventricular tachycardia

Arrhythmogenic cardiomyopathy is a non-ischaemic cardiomyopathy characterised by the presence of myocardial dysfunction and inherited conduction disease that predisposes patients to malignant ventricular arrhythmias and sudden cardiac death. There is a growing awareness of the diverse phenotypic presentation of arrhythmogenic cardiomyopathy, which may demonstrate preferential involvement of the left, right or both ventricles. A subset of arrhythmogenic cardiomyopathy may be due to mutations of desmosomes, intercellular junctions of the myocardium that promote structural and electrical integrity. Mutations of desmoplakin, encoded by the DSP gene and a critical constituent protein of desmosomes, have been implicated in the onset of arrhythmogenic cardiomyopathy. We present a structured case report of desmoplakin arrhythmogenic cardiomyopathy secondary to novel heterozygous DSP mutations (c.1061T>C and c.795G>C) manifesting as early onset non-ischaemic cardiomyopathy and recurrent ventricular tachycardia refractory to multiple modalities of therapy, including oral antiarrhythmics, cardiac ablation and bilateral sympathectomy, as well as frequent implantable cardioverter-defibrillator discharges.