Over half of SADS deaths were likely to be due to inherited heart disease; accurate identification is vital for appropriate prophylaxis amongst relatives who should undergo comprehensive cardiological evaluation, guided and confirmed by mutation analysis.

By using current diagnostic criteria, familial disease was present in 28% of index patients. A further 11% of their relatives had minor cardiac abnormalities, which, in the context of a disease whose mode of inheritance is autosomal dominant, are likely to represent early or mild disease expression. We advocate that the current ARVC diagnostic criteria are modified to reflect the broader spectrum of disease that is observed in family members.

Background-Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial heart muscle disease characterized by structural, electrical, and pathological abnormalities of the right ventricle (RV). Several disease loci have been identified. Mutations in desmoplakin have recently been isolated in both autosomal-dominant and autosomal-recessive forms of ARVC. Primary left ventricular (LV) variants of the disease are increasingly recognized. We report on a large family with autosomal-dominant left-sided ARVC. Methods and Results-The proband presented with sudden cardiac death and fibrofatty replacement of the LV myocardium. The family was evaluated. Diagnosis was based on modified diagnostic criteria for ARVC. Seven had inferior and/or lateral T-wave inversion on ECG, LV dilatation, and ventricular arrhythmia, predominantly extrasystoles of LV origin. Three had sustained ventricular tachycardia; 7 had late potentials on signal-averaged ECG. Cardiovascular magnetic resonance imaging in 4 patients revealed wall-motion abnormalities of the RV and patchy, late gadolinium enhancement in the LV, suggestive of fibrosis. Linkage confirmed cosegregation to the desmoplakin intragenic marker D6S2975. A heterozygous, single adenine insertion (2034insA) in the desmoplakin gene was identified in affected individuals only. A frameshift introducing a premature stop codon with truncation of the rod and carboxy terminus of desmoplakin was confirmed by Western blot analysis. Conclusions-We have described a new dominant mutation in desmoplakin that causes left-sided ARVC, with arrhythmias of LV origin, lateral T-wave inversion, and late gadolinium enhancement in the LV on magnetic resonance images.

SUMMARY In studies of the right ventricle the complexities of chamber shape may be overcome by use ofmultiple tomographic imaging planes. An established protocol for the echocardiographic description of the heart was used to examine the right ventricle in an ordered series of transducer locations and orientations. Diastolic measurements were made ofthe right ventricular inflow tract, outflow tract, and right ventricular body, and the range and reproducibility of normal values for cavity size and right ventricular free wall thickness were established. These measurements of cavity size in 41 normal subjects were highly reproducible and the views that were used correctly described the truncated and ellipsoidal shape of the right ventricular inflow tract and body with a separately aligned outflow tract. Cavity trabeculation prevented measurement of the free wall thickness in some areas; however, values of nearly twice the previously reported upper limit of normal for anterior regions were measured from the apex or lateral right ventricular wall.These normal data provide a basis for future echocardiographic studies of the right ventricle.