Familial dilated cardiomyopathy: evidence for clinical and immunogenetic heterogeneity.
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
Bilińska
Zofia T
ZT
Department of General Cardiology, Institute of Cardiology, Warsaw, Poland.
Michalak
Ewa
E
Piatosa
Barbara
B
Grzybowski
Jacek
J
Skwarek
Mirosław
M
Deptuch
Tomasz W
TW
Kuśmierczyk-Droszcz
Beata
B
Piotrowski
Walerian
W
Ruzyłło
Witold
W
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
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains