Episodic Myocardial Injury: Consider Desmoplakin Cardiomyopathy!

Abstract

<h3>Introduction</h3> Recurrent myopericarditis, characterized by repeated episodes of pericardial and myocardial inflammation, can be a diagnostic conundrum. We present one such case ultimately found to have a desmoplakin (DSP) gene mutation. <h3>Case Report</h3> Our patient was a previously well adolescent male with a several year history of episodic chest pain and significant troponin elevation. He had mild left ventricular (LV) systolic dysfunction by echocardiography, with no ventricular dilation, pericardial effusion or valvar dysfunction. He had intermittent ventricular bigeminy. Coronary arteries were normal. Cardiac MRI revealed late gadolinium enhancement involving the anterior and lateral LV walls and interventricular septum. Myocardial biopsy revealed patchy interstitial fibrosis. Genetic testing revealed a likely pathogenic DSP mutation, c.123C>G (p.Tyr41*), predicted to cause loss of normal protein function. The variant is uncommon in the general population and several downstream nonsense variants have been associated with cardiomyopathy, supporting pathogenicity. <h3>Summary</h3> DSP is an essential protein in desmosomes, intercellular complexes responsible for maintaining cell-cell adhesion. Desmosomal mutations can cause arrhythmogenic cardiomyopathy, in which cardiac myocytes undergo fibroadiposis resulting in ventricular dysfunction, arrhythmias and sudden death. New evidence supports that DSP mutations can cause an inflammatory phenotype distinct from typical arrhythmogenic cardiomyopathy, characterized by predominant LV involvement, recurrent episodes of myocardial injury and fibrosis preceding systolic dysfunction. Our patient fits the novel description of DSP cardiomyopathy. His management plan includes reverse remodeling agents, surveillance for arrhythmia and cardiac dysfunction, restriction from competitive sports, and cascade genetic screening. Our case highlights the role of cardiomyopathy/arrhythmia genetic panels in patients with recurrent, unexplained myocardial inflammation.