Prevalence and characteristics of dystrophin defects in adult male patients with dilated cardiomyopathy

OBJECTIVES To assess the prevalence of dystrophin defects in dilated cardio myopathy (DCM) in male patients and to formulate investigation strategies f or their identification. BACKGROUND Dystrophin defects presenting with predominant or exclusive card iac involvement may be clinically indistinguishable from "idiopathic" DCM. Diagnosis may be missed, unless specifically investigated. METHODS Clinical and biochemical evaluation, right ventricular endomyocardi al biopsy (EMB), light and electron microscopic and immunohistochemical stu dies of biopsy samples, six multiplex and two single polymerase chain react ions for 38 exons and automated sequencing of exon 9 and muscle promoter-ex on 1 were undertaken in 201 consecutive male patients presenting with DCM, with (n = 14) and without (n = 187) increased serum creatine phosphokinase (sCPK). RESULTS Dystrophin defects were identified in 13 of the 201 patients (6.5%, age 16-50). Family history was positive in four patients. Serum CPK levels were increased in 11 of 13 patients. Light microscopy examination of EMB w as uninformative; ultrastructural study showed multiple membrane defects. D ystrophin immunostain was abnormal. Eight patients, all older than 20, had deletions affecting midrod domain, normal or mildly increased CPK and bette r outcome than the five remaining cases all younger than 20, with more than five-fold increase of sCPK. Two of these latter had proximal and rod-domai n deletions. Sisters of two patients were diagnosed as noncarriers with mic rosatellite analysis. CONCLUSIONS Although the overall prevalence of dystrophin defects in our co nsecutive DCM male series is low (6.5%), immunohistochemical and molecular studies are essential to identify protein and gene defects; screening studi es are justified to define prevalence, clinical profile and genotype-phenot ype correlation. (J Am Col Cardiol 2000;35:1760-8) (C) 2000 by the American College of Cardiology.