Isolated JUP Plakoglobin Gene Mutation with Left Ventricular Fibrosis in
Familial Arrhythmogenic Right Ventricular Cardiomyopathy
Abstract
Introduction: Arrhythmogenic Right Ventricular Cardiomyopathy
(ARVC) is a rare inherited disorder usually affecting the right
ventricle (RV), characterized by fibro-fatty tissue replacement of the
healthy ventricular myocardium. It often predisposes young patients to
ventricular tachycardia, heart failure, and / or sudden cardiac death.
However, recent studies have suggested predominantly left
ventricle (LV) involvement with variable and / or atypical
manifestations. Cardiac Magnetic Resonance (CMR) imaging has emerged as
the non-invasive gold standard for the diagnosis of ARVC. Case
summary: A 21-year-old athletic male with a family history of unknown
ventricular arrhythmias, presented with near syncope, chest pain and
exertional palpitations. He had an initial work-up that was grossly
unremarkable including, electrocardiography (ECG), echocardiography and
CMR imaging. Six months later, he presented again with recurrent
symptoms during exercise and his ECG demonstrating a new epsilon wave.
He had markedly elevated cardiac biomarkers, (troponin I
>100 ng/dl, normal value < 0.04 ng/dl). A
subsequent coronary angiogram was performed, which was normal. Holter
monitoring further showed subsequent episodes of ventricular tachycardia
with a right bundle branch morphology. An endomyocardial biopsy was
performed, which was negative. A follow-up CMR demonstrated the
new development and prominent left ventricular epicardial scar
in the lateral wall. The patient underwent familial genetic testing,
which confirmed the presence of an isolated JUP gene mutation and showed
multiple genes consistent with ARVC in his mother. Thus, he manifested a
partial transmission of only one abnormal gene for ARVC and exhibited a
markedly different expression in his disease without evidence of typical
right-sided heart pathology. A third CMR study was performed, which
showed partial improvement in myocardial fibrosis after exercise
cessation. Conclusion: We present a case of a young male with a
newly diagnosed isolated JUP gene mutation and a genetically diagnosed
family history of ARVC. During his course, he demonstrated the
progression of a characteristic epsilon wave on ECG and the presence of
new, atypical, left ventricular fibrosis on repeat CMR imaging.
This case demonstrates a complex interplay between variable genetic
penetrance, phenotypical heterogeneity, and lifestyle factors including
exercise, in his disease expression and provides insight on the natural
course of an isolated JUP mutation. Although rare, clinicians should
have a high threshold for the suspicion of ARVC or variants of this
disorder even in the absence of classic right sided pathologies and /or
an initially normal work-up.