19 Molecular Genetics of Dilated Cardiomyopathy

Abstract

Cardiomyopathies are defined as diseases of the myocardium associated with cardiac dysfunction. According to the WHO/ISFC criteria, cardiomyopathies in human beings are classified by the major pathophysiology as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and right ventricular cardiomyopathy (Richardson et al. 1996). In dogs, dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are the most common inherited forms of myocardial disease. CANINE FAMILIAL CARDIOMYOPATHIES Familial Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is a primary myocardial disease characterized by cardiac enlargement and impaired contractile function of one or both ventricles. Although canine DCM is traditionally discussed as one disease, significant variation in the age of onset, presenting complaint, clinical features, and disease progression have been observed among and within breeds (Freeman et al. 1996; Tidholm and Jonsson 1996; Calvert et al. 1997; Kittleson et al. 1997; Brownlie and Cobb 1999; Meurs et al. 2001a,b; Sleeper et al. 2002), indicating the genetic diversity of DCM. The metabolic basis remains unknown, but deficiencies in myocardial L-carnitine in boxers (Keene et al. 1991) and taurine in American cocker spaniels (Kittleson et al. 1997) have been observed. DCM is generally seen in large and medium-sized adult dog breeds. Some breeds are clearly overrepresented, and this seems to vary some-what with geographical location. In North America, the Doberman pinscher, Irish wolfhound, Great Dane, and American cocker spaniels are among the most commonly reported breeds (Monnet et al. 1995; Sisson et al. 2000). Some European references suggest an increased incidence in the Airedale terrier, Doberman pinscher, Newfoundland, and English...