Dilated cardiomyopathy is characterized by an increase in left ventricular end-diastolic diameter (>2.7 cm/m2) and reduced left ventricular systolic function (ejection fraction of <0.45). Dilated cardiomyopathy is among the most common causes of heart failure in the young and a major reason for cardiac transplantation. The overall prevalence of DCM in the U.S. is 36.5/100,000. About 35% to 50% of cases have a positive family history. In addition, about 10% of asymptomatic relatives of probands with DCM have evidence of unrecognized left ventricular dysfunction. Every inheritance pattern has been noted, including autosomal dominant and recessive, X-linked, and maternal (mitochondrial) forms, although the autosomal dominant forms are the most common.
Familial dilated cardiomyopathy (FDCM) can be further divided into 2 subtypes—isolated FDCM and FDCM with cardiac conduction defects. Both exhibit genetic heterogeneity, as over a dozen different chromosomal loci have been mapped to contain DCM-related genes. Mutations in several genes have been associated with isolated (pure) DCM, including the genes encoding cardiac actin, desmin, γ-sarcoglycan, β-sarcoglycan, cardiac troponin T, α-tropomyosin, β-myosin heavy chain, and cardiac myosin-binding protein C gene. Mutations in many of the genes that cause DCM also can cause HCM, as illustrated by mutations in β-myosin heavy chain and cardiac troponin T
Genes Associated With Cardiomyopathy
| Disorder | Inheritance Pattern | Gene Product |
|---|---|---|
| DCM | ||
| Pure familial DCM | AD | actin |
| AD | desmin | |
| AD | γ-sarcoglycan | |
| AD | tropinin T | |
| AD | β-myosin heavy chain⁎ | |
| AD | CSRP3 | |
| AD | phospholamban | |
| (1 case) | TCAP | |
| DCM with ventricular tachycardia | (2 cases) | ABCC9 |
| DCM with wooly hair and keratoderma | AR | desmoplakin |
| DCM plus cardiac conduction defects (Emery-Dreifuss muscular dystrophy) | AD | lamin A/C⁎ |
| X-linked DCM (Duchene/Becker muscular dystrophy) | XLR | dystrophin⁎ |
| X-linked DCM (also Barth syndrome, isolated noncompaction of the ventricular myocardium) | XLR | tafazzin⁎ |
| Isolated noncompaction of the ventricular myocardium | AD | α-dystrobrevin |
| AD | Cypher/ZASP | |
| AD | lamin A/C⁎ | |
| HCM (192600) | ||
| HCM | AD | α-tropomyosin⁎ |
| AD | cardiac myosin-binding protein C⁎ | |
| AD | β-myosin heavy chain⁎ | |
| AD | tropinin T | |
| AD | myosin light chain | |
| AD | cardiac troponin I | |
| AD | myosin light chain 3 | |
| AD | titan | |
| AD | myosin heavy chain-α | |
| Mito | tRNA-glycine | |
| Mito | tRNA-isoleucine | |
| HCM and DCM | ||
| Primarily causes HCM; only 1 patient with DCM | AD | cardiac myosin-binding protein |
| AD | β-myosin heavy chain⁎ | |
| AD | actin | |
| AD | cardiac myosin light-peptide kinase | |
| AD | caveolin-3 | |
| AD | α-tropomyosin | |
| Arrythmogenic right ventricular dysplasia | ||
| AD | ryanodine receptor | |
| AD | desmoplakin | |
| AD | plakophilin 2 |
AD = autosomal dominant; AR = autosomal recessive; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; Mito = mitochondrial; XLR = X-linked recessive.
Clinical testing is available.
