Conclusion:
We present a case of a young male with a family history of ventricular arrhythmias, who had two separate hospitalizations for pre-syncope with the manifestations of ARVC including the development of an epsilon wave on ECG along with atypical, left sided myocardial dysfunction and the development of left ventricular fibrosis on repeat CMR scan. He was found to have an isolated JUP mutation with other family members having multiple abnormal genes for ARVC. The timing and manifestations of these findings over two separate hospitalizations have been seldom reported, particularly with only any isolated JUP mutation. Since its discovery, ARVC has undergone an evolution in diagnostic criterion due to it variability in presentation and manifestations, as well as the discovery of a broad spectrum and interplay of genes. Clinicians should recognize the disease heterogeneity, as demonstrated in our case, particularly where the initial cardiac work-up including his initial CMR study and endomyocardial biopsy was unremarkable. Finally, this case provides insight into the potential complex interplay in genotype and lifestyle factors in the expression of an isolated JUP mutation, and its involvement in various arrhythmogenic cardiomyopathies.