Arrhythmogenic cardiomyopathy in children, on the link between injurious mutations and inflammation: Two case reports and review of the literature

BACKGROUND In this case report, we aimed to raise awareness regarding arrhythmogenic cardiomyopathy (ACM) with inflammatory “hot phase” episodes in pediatric patients, which is often misdiagnosed as myocarditis. This condition, caused by aseptic intracellular inflammation, can be misdiagnosed as acute coronary syndrome or myocardial viral infection, with the latter being particularly common in children. Here, we report two pediatric cases of ACM with “hot phase” episodes and discuss the molecular mechanisms leading to aseptic myocardial inflammation due to desmosome and cytoskeletal damage. CASE SUMMARY The first patient (aged 13 years) was hospitalized after experiencing a single episode of syncope, chest pain, and palpitation. Clinical examination revealed elevated troponin levels, complete right bundle branch block, right ventricular dilation, and normal coronary arteries. Cardiac magnetic resonance imaging (MRI) revealed extensive fibrotic changes in the right ventricle, which was consistent with ACM, and a pathogenic variant in DSG2 confirmed the diagnosis. The second patient (aged 4 years) presented with chest pain and elevated troponin levels. Electrocardiography revealed a left bundle branch block, while echocardiography showed reduced left ventricular contractility. Cardiac MRI demonstrated left ventricular dilation and subepicardial fibrosis. The phenotypic features, such as curly-wool hair, hyperkeratosis, and onychodystrophy, suggested a genetic nature of the disease. Two mutations identified in DSP confirmed the diagnosis of Carvajal syndrome with intermittent “hot phase” episodes. CONCLUSION ACM in children can present with nonspecific inflammatory symptoms, which may be misdiagnosed as myocarditis or coronary artery pathology.