Myocarditis Revealing a Pathogenic Desmoplakin (DSP) Variant: Implications for Genetic Testing Pathways

Desmoplakin (DSP) variants are associated with arrhythmogenic cardiomyopathy and can present with myocarditis-like "hot phases" before overt structural disease develops. We report a 30-year-old woman who presented with chest tightness, palpitations, and elevated troponin and was diagnosed with acute myocarditis on cardiac magnetic resonance imaging. In view of a family history of myocarditis in her younger sister, genomic testing was pursued following multidisciplinary review, despite the absence of a dedicated myocarditis testing pathway. A pathogenic heterozygous DSP splice-site variant (c.939+1G>A) was identified and was also detected in her asymptomatic father, who had a normal cardiac phenotype. Over the following 16 months, the patient experienced eight further episodes of myocarditis-like symptoms, resulting in nine episodes in total. These were characterized by recurrent chest pain and mild troponin elevation with minimal or no elevation of inflammatory markers, while biventricular systolic function remained preserved. This case illustrates recurrent myocarditis as a potential early manifestation of DSP-related cardiomyopathy, including in the absence of global systolic dysfunction. It also highlights the diagnostic value of genomic testing in patients with recurrent myocarditis, particularly in the presence of a relevant family history. Identification of a pathogenic DSP variant can inform longitudinal surveillance, prognostic assessment, and cascade screening of relatives and supports consideration of clearer genomic testing pathways for selected patients presenting with recurrent myocarditis.