Familial effort polymorphic ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy map to chromosome 1q42-43

In the present study we report on another cause of an arrhythmia associated with familial arrhythmogenic right ventricular cardiomyopathy (ARVC), whic h is linked to chromosome 1q42-43, Two families with 48 subjects were studi ed with 12-lead electrocardiography, 24-hour ambulatory electrocardiography , chest x-ray, M-mode and 2-dimensional echocardiography, signal-averaging electrocardiography, and exercise stress testing, Six subjects also underwe nt right and left ventricular angiography and electrophysiologic study. An endomyocardial biopsy was performed in 1 subject. The genetic study include d pedigree reconstruction and linkage analysis with polymorphic DNA markers . Five young subjects died suddenly during exercise; autopsy was performed in 3 and showed segmental fibro-fatty replacement of the right ventricle, m ostly at the apex. Two of them experienced syncopal attacks during effort. polymorphic ventricular arrhythmias during effort; ARVC was diagnosed in 15 , whereas 1 did not have any demonstrable cardiac abnormality, The remainin g family members were healthy and did not have arrhythmias. The linkage stu dy assigned the disease locus to chromosome 1q42-q43, in close proximity to the alpha-actinin 2 locus (maximal lod score was 5.754 at theta = 0) with a 95% penetrance. Thus, these data suggest that effort-induced polymorphic ventricular arrhythmias and juvenile sudden death can be due to adrenergic stimulation in a particular genetic group of ARVC patients. In these cases the pathology was segmental, mostly localized to the right ventricular apex . Ventricular arrhythmias that are present in these families differ from th e monomorphic ones that are usually seen in patients with ARVC. (C)2000 by Excerpta Medica, Inc.