Frequency of RCM

RCM is the least common of the cardiomyopathies, accounting for just 5 percent of the total. However, RCM has the worst prognosis and poorest therapeutic options. In a study by Dr. Jeffrey Towbin and colleagues at Texas Children’s Hospital, 28 percent of children with RCM succumbed to sudden cardiac death, usually within one year of diagnosis; the underlying mechanisms causing heart failure were usually ischemia-related. The frequency of familial RCM is unknown, but when it occurs, there is usually associated atrioventricular block and skeletal myopathy, although some cases without conduction disease or skeletal myopathy have been reported.

Causes of RCM

RCM can be idiopathic (cause unknown) or secondary to a number of rare cardiac and systemic disorders such as endomyocardial fibrosis, infiltrative disorders (amyloidosis, sarcoidosis), and rare metabolic disorders (Gaucher's disease, mucopolysaccharidoses, Fabry's disease, carcinoid syndrome).

Patients with the idiopathic form may have a family history of cardiomyopathy. Recent evidence suggests that the disease may be caused by the same genetic abnormalities that result in the more common hypertrophic cardiomyopathy.

Familial RCM

All hereditary information is transmitted through DNA, which encodes many genes (approximately 100,000) that are transcribed to make specific proteins. Inherited disorders due to a single abnormal gene are transmitted to offspring in a predictable fashion, termed Mendelian transmission. As a result of gene mutations, abnormal genes located on any of the 22 autosomal pairs or the two sex chromosomes may produce phenotypes inherited by simple patterns classified as autosomal (dominant or recessive) or X-linked, respectively. When different genes induce the same phenotype, it is referred to as genetic heterogeneity, and most diseases in humans exhibit genetic heterogeneity. Families with multiple individuals who have RCM are likely to have a genetically inherited form, termed familial RCM. However, not all affected individuals, however, must have an affected parent because, in all autosomal dominant diseases, a certain proportion of cases occur due to a new mutation (i.e., they are sporadic). The parent whose germ cells contain the new mutation will be clinically normal, since the mutation affects only a single germ cell, but can transmit the disease-causing allele to their offspring.

Etiologically, amyloid accumulation has been considered the most common cause of RCM, particularly in the elderly. Genetic variants of the plasma protein transthyretin (prealbumin) have been shown to cause inherited forms of amyloidosis associated with cardiomyopathy. Accumulation of the muscle-specific intermediate filament desmin, has also been found in patients with a complex phenotype that includes RCM, AV block, and skeletal myopathy by immunohistochemistry, while mutations in the desmin gene, have been found in patients with RCM, dilated cardiomyopathy, or hypertrophic cardiomyopathy, with skeletal myopathy. These conditions have now been termed desminopathies or desmin myopathies. Further, mutations of desmin in mice result in similar clinical phenotypes. Recently, mutations in cardiac troponin I were identified.