Abstract 3448: Cardiac Dystrophinopathies: Prevalence and Clinical Phenotypes in a Consecutive Series of 408 Males with Idiopathic Dilated Cardiomyopathy
Dystrophin gene (DYS) defects cause three major clinical phenotypes: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy (DCM). In the cardiology setting patients come to the clinical attention for DCM with/without increased serum creatine phosphokinase (sCPK) and/or myopathy. Purpose To determine the prevalence of DYS defects in a consecutive series of 408 DCM patients and to describe their phenotypes.
Methods DCM was diagnosed according to WHO criteria. The criterion for first level DYS screening was male sex: we included males with both normal and increased sCPK. The criterion for second level DYS screening was the presence of defects of myocyte immunostaining by 5′, rod, midrod and C-terminal domain using anti-DYS antibodies at endomyocardial biopsy. This latter analysis consisted of the direct automated sequencing of the 75 exons and flanking regions of the gene.
Results We identified DYS defects in 31 of the 408 probands (7.6%); the defects were exon deletions in 29 and point mutations in 2 cases. The former were single exon deletions in 4/31 (13%); multiple contiguous exon deletions in 18/31 (58%) and multiple non contiguous deletions in 7/31 (22.5%). The point mutations were a splice site mutation in 1 and a stop mutation in one. The mean age at clinical presentation was 34±15 years. The 31 probands shared a typical DCM phenotype. Seven (22.5%) patients had a confounding recent history of a flu-like episodes that suggested a myocarditis. Twenty-six (84%) had associated increased sCPK; 19 (61%) had clinical evidence of BMD. All were inherited: the mother were healthy (n=28) or showed a mild late onset DCM phenotype (n=3). Three patients underwent cardioverter defibrillator implantation (ICD) on the basis of the presence of severely impaired left ventricular ejection fraction (<30%). During 80±41 months of follow-up, 8 (26%) patients underwent heart transplantation, 3 (9.6%) patients died with end-stage heart failure; none had appropriate ICD interventions or died suddenly.
Conclusions We confirm the prevalence of about 8% of DYS defects in male patients with DCM. The recurrent markers are DCM with end-stage heart failure evolution, low arrhythmogenic risk and increased sCPK (61%).