Cardiomyopathy in Childhood: Histopathological and Genetic Features

Primary heart muscle disease is a cause of significant morbidity and mortality in childhood. The current WHO classification of cardiomyopathy is based on a combination of clinical features, aetiology and pathology. It is in need of revision because of accumulating genetic information concerning the pathogenesis of cardiomyopathy. It is becoming increasingly obvious that most of the primary heart muscle diseases have a genetic origin. Mutations in the genes encoding the sarcomeric proteins are responsible for hypertrophic cardiomyopathy and some forms of dilated and restrictive cardiomyopathy. Other forms of dilated cardiomyopathy are caused by mutations in genes encoding cytoskeletal proteins. Arrhythmogenic right ventricular cardiomyopathy is now known to be caused by mutations in genes involved in cell cohesion. Gene mutations affecting mitochondrial function can cause cardiomyopathy, either as part of a systemic disorder, or confined to the heart. Gene mutations causing rarer forms of cardiomyopathy associated with abnormalities of cardiac rhythm, such as histiocytoid cardiomyopathy and ventricular non-compaction have also been identified. This review details the pathology of cardiomyopathy and the increasing number of genes involved in its aetiology and pathogenesis. Genetic analysis not only permits diagnosis in many cases but also in an increasing number of the cardiomyopathies provides prognostic information.