Inflammatory Features in Homozygous DSG2 Cardiomyopathy Mimicking Cardiac Sarcoidosis

Homozygous variants in DSG2, a desmosomal protein, are associated with a severe form of biventricular arrhythmogenic cardiomyopathy (ACM). To date, myocardial inflammation mimicking isolated cardiac sarcoidosis (CS) and responding well to immunosuppressive therapy (IST) has not been described in this entity.

A young man with sustained ventricular tachycardia was diagnosed with ACM. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography raised suspicion on isolated CS with left ventricular inflammation. Endomyocardial biopsies only showed interstitial fibrosis. Empirical IST with corticosteroids and azathioprine reduced inflammation and led to flare-ups when tapered. Post-transplant histology showed no granulomas, but extensive fibrofatty replacement typically seen in ACM. Genetic testing identified a novel homozygous DSG2 variant (DSG2 c.523+2T>C (splice donor)).

IST may be effective in controlling inflammation, arrhythmias, and disease progression in severe desmosomal disease.

We highlight the presence of severe biventricular ACM associated with a novel homozygous DSG2 variant with chronic inflammatory features mimicking CS responding to IST.