Work

Inflammatory Features in Homozygous DSG2 Cardiomyopathy Mimicking Cardiac Sarcoidosis

Year: 2025

Type: article

Abstract: BACKGROUND: 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. CASE SUMMARY: 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)). DISCUSSION: IST may be effective in controlling inflammation, arrhythmias, and disease progression in severe desmosomal disease. TAKE-HOME MESSAGE: We highlight the presence of severe biventricular ACM associated with a novel homozygous DSG2 variant with chronic inflammatory features mimicking CS responding to IST.

Source: JACC Case Reports

DOI: 10.1016/j.jaccas.2025.105345