Clinical genetics of dilated cardiomyopathy

The pathogenesis of dilated cardiomyopathy (DCM) remains controversial. Over the last few years there has been a gradual accumulation of evidence suggesting that familial forms of DCM are common and are most likely due to the transmission of a rare autosomal dominant gene. Despite these observations absolute proof that familial DCM is genetic is not available and there are many unanswered questions about the molecular basis of familial DCM. Is familial DCM caused by a single rare genetic defect or are there a number of genes involved which can be transmitted by different mechanisms? What factors govern whether an individual with an abnormal gene develops clinical DCM? Do individuals with mild echocardiographic abnormalities have early DCM? By performing linkage analysis on large informative families with familial DCM clinical cardiologists and geneticists should be able to address these and other important questions. Identification of the gene, or genes, responsible for familial DCM promises to permit reliable preclinical diagnosis to be made and enable unrecognised carriers of the condition to be identified. In addition to the impact this will have on genetic counselling and on our understanding the broader topic of pathogenesis, this will have important consequences for clinicians. Knowing a family member is genetically affected but preclinical will allow treatment to be started early in the natural history of the disease and new treatment strategies specifically against DCM to be developed. We are optimistic that the application of molecular biological techniques to the clinical genetics of DCM heralds the beginning of a new era in our understanding and treatment of this condition.