Aspetti clinici e genetico molecolari delle cardiomiopatie mitocondriali. Necessità di un approccio multispecialistico

Cardiomyopathies are a heterogeneous group of disorders affecting primarily myocardium. The high frequency of familiar cases has suggested underlying genetic factors. Among the first pathogenic mutations so far established, are those regarding genes encoding contiactile and structural sarcomeric proteins, such as β-myosin heavy chain (MYH7). However, such defects are disclosed in less than 50% of familial cases. Cardiomyopathy, usually associated to other signs of skeletal muscle and nervous tissue involvement, has been frequently reported in mitochortdrial diseases, which are multisystem disorders. Defects of energy production systems such as oxidative phosphorilation are likely to affect the heart, which is heavily dependent on oxidative metabolism. We recently started a retrospective and prospective study on patients with cardiomyopathy as unique or predominant clinical feature. Mitochondrial biochemical and/or morphologic abnormalities in muscle or heart and maternal inheritance were inclusion criteria. Soon two pathogenic mutations of mitochondrial DNA (mtDNA) have been discovered. One family with juvenile onset restrictive-hypertrophie cardiomyopathy over four generations harbored a mutation in the 12S rRNA gene (A1555G). A novel point mutation in tRNA He(A4300G) was found in another family with pure hypertrophie cardiomyopathy. The occurrence of isolated cardiomyopathies reinforces the concept of the wide heterogeneity of clinical presentations associated to mtDNA mutations. Potentially all medical specialists, not only neurologists, should be involved in diagnosing and managing mitochondrial diseases. Close collaboration between neurologists and other specialists is recommended not only for a better definition of these diseases and for obvious counseling reasons, but also for a more rational approach to possible therapies.