Familial dilated cardiomyopathy (DCM) should be an "evidence-based" diagnosis derived from clinical and echocardiographic screening of informed and consenting relatives of index patients, and on the examination of clinical reports for deceased relatives. Most
familial dilated cardiomyopathy pedigrees show an autosomal pattern of inheritance. Very few of them are X-linked and matrilinear. Autosomal recessive inheritance is difficult to be assessed in an evidence-based setting. By linkage analysis, several loci, but no disease gene, have been identified. At present, few cases of
familial dilated cardiomyopathy can benefit of a molecular diagnosis. The diagnosis of
dystrophin defect-related
dilated cardiomyopathy is important for patients and families, especially for carrier detection. These patients present X-linked inheritance, dominant cardiac involvement and raised levels of serum
creatine phosphokinase. Defects of the
glycoprotein complex associated to
dystrophin (DAG) are rare skeletal muscle diseases with possible cardiac involvement.
Mitochondrial diseases, both pure
cardiomyopathies and multiorgan syndromes involving the heart, are associated to defects of
mitochondrial DNA genes or of nuclear genes coding for
mitochondrial proteins. Barth's syndrome develops in male children with
granulocytopenia,
dilated cardiomyopathy, and methylglutaconic aciduria.
Cardiomyopathies with
atrioventricular block are observed in
hemochromatosis,
Emery-Dreifuss syndrome,
desmin storage disease, and in isolated
familial dilated cardiomyopathy. Actin defects were recently identified in 2 unrelated patients with
familial dilated cardiomyopathy.
Desmin defects were also recently identified in 1
familial dilated cardiomyopathy. The overall knowledge, although in progression, is still limited. Clinical family screening identifies familial forms, preclinical cases, and inheritance pattern. By candidate gene screening, the molecular diagnosis can be provided for
dystrophin, DAG,
mitochondrial DNA, actin and
desmin gene defects.