Desmoplakin Cardiomyopathy Presenting as Recurrent Myocarditis Treated With Immunosuppression

Desmoplakin (DSP) cardiomyopathy is a genetic cardiomyopathy which causes myocarditis, heart failure, and sudden death.

A 42-year-old female presented with palmoplantar keratoderma, recurrent magnetic resonance imaging-confirmed myocarditis, and intense inflammation on cardiac positron emission tomography. Genetic testing confirmed DSP cardiomyopathy with a novel heterozygous DSP c.123C>G (p.Tyr41∗) truncating variant. Immunosuppression with prednisone and mycophenolate mofetil produced marked improvement on repeat positron emission tomography imaging. Predictive testing identified the same mutation in her 44-year-old sister. Cardiac magnetic resonance imaging revealed occult cardiomyopathy with severe myocardial fibrosis of similar phenotype. Both patients received heart failure therapies and were offered primary prevention implantable cardioverter defibrillator.

A novel DSP truncating variant associated with inflammatory cardiomyopathy was identified. We propose a treatment algorithm to manage DSP cardiomyopathy incorporating predictive testing of relatives, immunosuppression of myocardial inflammation, risk stratification of sudden death, and initiation of heart failure therapies.

We present a novel DSP variant and algorithm to manage DSP cardiomyopathy.