title: Familial dilated cardiomyopathy: evidence for clinical and immunogenetic heterogeneity.
abstract: BACKGROUND
  There is increasing awareness of the familial nature of dilated cardiomyopathy (DCM). Mutations in the genes coding for cytoskeletal and sarcomere proteins have been identified. Phenotyping of familial DCM (FDCM) may help to improve genetic diagnosis. The aim of our study was to evaluate the clinical features, pattern of transmission, and immunogenetic data of FDCM.
  
  
  METHODS
  We obtained family histories in order to construct pedigrees and prospectively evaluated 204 family members of 27 patients with angiographically proven DCM. FDCM was defined as more than 1 person with DCM in a family. The study protocol included repeated clinical examination, electrocardiography, echocardiography and blood sampling.
  
  
  RESULTS
  Among the families, we identified the following phenotypes: DCM with conduction defects (n=2), early onset DCM with a rapid course in male relatives (n=2), and DCM preceded by ventricular arrhythmia (n=1). The remaining families presented with a heterogeneous course of the disease. The disease was transmitted in an autosomal dominant fashion in 14 of our pedigrees, possibly X-linked in three and indeterminate in 10 sib-pairs. The frequency of the DRB1*04 allele was low in probands with the disease (3/20, 15%); heterozygozity for DRB1*03/DRB1*04, known to increase susceptibility to IDDM1, was identified in 2 of 20 DCM probands (10%).
  
  
  CONCLUSIONS
  Familial dilated cardiomyopathy is a heterogeneous disorder; autosomal dominant transmission is most common. The distinct clinical phenotypes and specific immunogenetic features found in some families indicate that different pathogenetic mechanisms can lead to the
authors.affiliation: Department of General Cardiology, Institute of Cardiology, Warsaw, Poland.
authors.forename: Zofia T
authors.initials: ZT
authors.lastname: Bilińska
authors.forename: Ewa
authors.initials: E
authors.lastname: Michalak
authors.forename: Barbara
authors.initials: B
authors.lastname: Piatosa
authors.forename: Jacek
authors.initials: J
authors.lastname: Grzybowski
authors.forename: Mirosław
authors.initials: M
authors.lastname: Skwarek
authors.forename: Tomasz W
authors.initials: TW
authors.lastname: Deptuch
authors.forename: Beata
authors.initials: B
authors.lastname: Kuśmierczyk-Droszcz
authors.forename: Walerian
authors.initials: W
authors.lastname: Piotrowski
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyłło
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D008040:Genetic Linkage; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007125:Immunogenetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains