Registry of families with inherited dilated cardiomyopathy for molecular analyses

Abstract

Despite several reports on the genetic cause of dilated cardiomyopathy (DCM), most cases are believed to be sporadic and specific clinical findings are not well defined. Therefore, we initiated a registry of patients with idiopathic DCM to analyze the frequency and clinical characteristics of this inherited disorder. In a first evaluation, 445 consecutive patients with angiographically proven DCM were included. Pedigrees were constructed, and 970 first and second-degree family members were examined. Familial DCM was confirmed in 48 (10.8%) of the 445 index patients and was suspected in 108 (24.2%) patients. Among the families of the 48 index patients with confirmed familial disease, five phenotypes (A—E) of familial DCM could be identified in 19 independent families: (A) 2 families with juvenile DCM with subclinical muscular dystrophy and elevated CK-MM levels, (B) 5 families with juvenile DCM without an increase of CK-MM, (C) 5 families with DCM and segmental hypokinesia of the left ventricle, (D) 6 families with DCM and early conduction defects, and (E) only 1 DCM family with sensorineural hearing loss. Genetic analyses of a DCM family with phenotype A revealed an X-linked inheritance. DNA and protein analyses identified a mutated rod region of the dystrophin gene to be associated with this rapidly progressive disorder in young males. The present results indicate that DCM may be a genetic disorder in approximately 35% of all cases. The common phenotypes of DCM may facilitate screening for genetic defects and help in risk stratification. In particular, young men with suspected DCM (phenotype A and B) show a rapid progression of the disease and should, therefore, be closely evaluated for heart transplantation.KeywordsMuscular DystrophyDilate CardiomyopathySensorineural Hearing LossIndex PatientDuchenne Muscular DystrophyThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.