Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 2 (4), 280-6

Current Perspective New Insights Into the Molecular Basis of Familial Dilated Cardiomyopathy

  • PMID: 11374497

Current Perspective New Insights Into the Molecular Basis of Familial Dilated Cardiomyopathy

G Sinagra et al. Ital Heart J.


Genetic disease transmission has been identified in a significant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, as well as recent molecular genetic data, indicate the existence of several genes causing the disease. Several distinct subtypes of familial DCM have been identified. Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene. This latter gene has recently been found to be responsible for both the autosomal dominant form of DCM with subclinical skeletal muscle disease (7.7% of cases) and the familial form with conduction defects (2.6% of cases) or the autosomal dominant variant of Emery-Dreifuss muscular dystrophy. The autosomal recessive form of DCM accounts for 16% of cases and is characterized by a worse prognosis. An X-linked form of DCM (10% of cases) manifests in the adult population and is due to mutations in the dystrophin gene. In the rare infantile form of DCM, mutations in the G4.5 gene have been identified. Finally, some of the rare unclassifiable forms (7.7% of cases) may be due to mitochondrial DNA mutations. Clinical and experimental evidence based on animal models suggest that, in a large number of cases, DCMs are diseases of the cytoskeleton. However, other causes, such as alterations in regulatory elements and in signaling molecules, are possible. Moreover, other genes called modifier genes can influence the severity, penetrance, and expression of the disease, and they will be a main objective of future investigations. Familial DCM is frequent, cannot be predicted on a clinical or morphological basis and requires family screening for identification. The advances in the genetics of familial DCM can allow improved diagnosis, prevention and genetic counseling, and represent the basis for the development of new therapies.

Similar articles

  • [Familial Dilated Cardiomyopathy]
    KJ Osterziel et al. Herz 30 (6), 529-34. PMID 16170685. - Review
    Dilated cardiomyopathy (DCM) is the most frequent form of primary myocardial diseases and the third most common cause of heart failure. Clinically, DCM is characterized b …
  • [Genetic Diagnosis of Familial Dilated Cardiomyopathy]
    M Pasotti et al. Ital Heart J Suppl 3 (4), 386-93. PMID 12025381. - Review
    The definition of familial dilated cardiomyopathy (DCM) is clinically based on the presence, in the same family, of at least two members proven as affected. The prevalenc …
  • Familial Dilated Cardiomyopathy: Evidence for Clinical and Immunogenetic Heterogeneity
    ZT Bilińska et al. Med Sci Monit 9 (5), CR167-74. PMID 12761452.
    Familial dilated cardiomyopathy is a heterogeneous disorder; autosomal dominant transmission is most common. The distinct clinical phenotypes and specific immunogenetic f …
  • Clinical Genetics of Dilated Cardiomyopathy
    PJ Keeling et al. Herz 19 (2), 91-6. PMID 8194837. - Review
    The pathogenesis of dilated cardiomyopathy (DCM) remains controversial. Over the last few years there has been a gradual accumulation of evidence suggesting that familial …
  • Anti-heart Autoantibodies in Familial Dilated Cardiomyopathy
    AL Caforio et al. Autoimmunity 41 (6), 462-9. PMID 18781472. - Review
    Familial aggregation is a feature of myocarditis and dilated cardiomyopathy (DCM). Myocarditis, a clinically polymorphic inflammatory disease of the myocardium, is diagno …
See all similar articles

Cited by 5 PubMed Central articles

Publication types

LinkOut - more resources