Evidence-based diagnosis of familial non-X-linked dilated cardiomyopathy: Prevalence, inheritance and characteristics

Aims: To assess the prevalence of familial non-X-linked dilated cardiomyopathy, to diagnose early asymptomatic cases evaluate inheritance and characterize clinical phenotypes. Methods and Results: We screened 472 relatives of-104 consecutive patients diagnosed with dilated cardiomyopathy; males with X-linked dilated cardiomyopathy were excluded based on systematic immunohistochemical and molecular analysis. Relatives underwent clinical examination, electrocardiography, echocardiography and serum creatine-phosphokinase determination. Twenty-six index patients (25%) had familial disease: four youths (≤20 years) had rapidly progressive outcome and underwent emergency transplantation. In a sib-pair, the onset was with atrioventricular block. Inheritance was autosomal dominant in 15, undetermined in seven (four sib-pairs); mitochondrial DNA pathological mutations were found in four. The screening identified 23 newly diagnosed relatives in the familial group. Transplantation (P=0.04) and atrial fibrillation (P=0.04) were more frequent, and left bundle branch block (P=0.04) less frequent in index patients with familial than in those with non-familial disease. Several non-affected relatives had instrumental abnormalities potentially useful as pre-clinical markers: their prevalence was similar in both groups. Conclusions: The prevalence of familial, non X-linked dilated cardiomyopathy was 25%. The immediate benefits of screening family members of index patients was early diagnosis in unaware symptomless affected relatives.