And the answer is a four-based mare deletion and frameshift in PKP2. So this young woman most likely has arrhythmogenic cardiomyopathy with right ventricular predominance. The prior name for this condition was arrhythmogenic right ventricular cardiomyopathy, and that name is still often used, although it is notable that the left ventricle is often involved, sometimes solely involved, but usually as the condition progresses, both ventricles become involved. For that reason, the condition has been renamed arrhythmogenic cardiomyopathy. Now, the fact that she is affected is based on the history, the transthoracic echo, which shows IV dilatation, and the abnormal electrocardiogram, which showed T-wave inversions V1 to V4 without a right bundle branch block. The PVCs are most likely of right ventricular origin with a left bundle branch block morphology. A cardiac MRI would be appropriate to more clearly define the structural and functional abnormalities of the right ventricle that are associated with the condition and to identify the presence and extent of fibrosis. Now, most cases of arrhythmogenic cardiomyopathy are caused by mutations in the desmosomal genes. The desmosomes are cardiac structures, membrane structures that hold cells together. Thus, the deletion frame shift in placofilin-2, PKP2, is the most likely cause. While mutations of desmoglion-2, DHT2, also cause arrhythmogenic cardiomyopathy, synonymous mutations in DNA do not change the protein. They don't change the DNA at a wobble base, but don't change the protein and rarely cause disease. Mutations in HERG cause long QT syndrome type 2. Mutations in TITAN cause dilated cardiomyopathy and are a consideration here, but less likely than the ARVC genes. Mutations in the ryanin receptor cause catecholaminergic polymorphic ventricular tachycardia. In arrhythmogenic cardiomyopathy, exercise restriction is important. The importance of restricting aerobic exercise is uncertain in most of the inherited arrhythmia syndromes, especially in those where arrhythmias are not triggered by an adrenergic stimuli or in patients where they are better treated with beta blockers. However, in arrhythmogenic cardiomyopathy, vigorous aerobic exercises both cause arrhythmias and may lead to more rapid progression of the condition. For this reason, high-level aerobic activity should be avoided. That said, some exercise remains good and people should not be told to do absolutely no exercise at all. The clinical diagnosis of arrhythmogenic cardiomyopathy and especially the right ventricular predominant type can be made based on a number of major and minor criteria. I've listed the citation here for the most recent versions of the criteria. They are made by a combination of right ventricular dilation and functional abnormalities by fibrous replacement of the right ventricle on histology. Note that fibrofatty replacement by MRI is no longer considered a criteria that is present in arrhythmogenic cardiomyopathy because fat in the myocardium is not in and of itself abnormal. Other considerations include repolarization abnormalities on the electric cardiogram, T-inversions in the right precordial leads, depolarization abnormalities on the ECG, specifically epsilon waves, which are diagnostic when present but not commonly present, and abnormalities on a signal average DKG, arrhythmias that are of right ventricular origin, and either a family history or the presence of confirmatory genetics. The clinical diagnosis is based on major and minor criteria. Each of these criteria that I've listed here can be major or minor depending on the severity of the abnormalities.

arrhythmogenic cardiomyopathy

PKP2 gene mutation

ventricular dilation

exercise restriction

desmosomal genes