Clinical and Molecular Study on Duchenne Muscular Dystrophy

Abstract

Background: Duchenne Dystrophy is the most common and severe form of muscular dystrophy. It has an X chromosome-linked recessive inheritance and affects boys’ striated muscles and myocardium. It is caused by mutations in the dystrophin gene, the largest human gene, composed of 79 exons. Objectives: To check the early cardiac changes in pediatric patients with Duchenne muscular dystrophy (DMD) and carry out the molecular study of changes in the dystrophin gene. Methods: Prospective study involving pediatric patients with DMD, with clinical assessment, measurement of serum levels of creatine phosphokinase, electrocardiogram, Doppler echocardiography and dynamic electrocardiography and DNA genotyping, with amplification of the 18 most affected exons. Results: A group of 11 boys aged 6-14 years was studied. Clinical cardiological examination did not reveal any major changes. An increase in creatinine phosphokinase was detected in all patients. Electrocardiogram showed early changes, with high R waves in V1 (n=7) right bundle branch block (n=2), delta waves and short PR interval (n=1), and signs of disturbance of ventricular repolarization (n=1). Echocardiogram showed signs of systolic dysfunction. Dynamic electrocardiogram (Holter) showed changes in 4 patients: with many extrasystoles (n=3) and Wolff-Parkinson-White syndrome (n=1). All children received corticosteroid therapy. There was no significant correlation between exon 52 deletion and arrhythmias (p=0.43). The molecular study revealed an exon 52 deletion in 4 patients with dilated cardiomyopathy, of which 2 had concomitant deletion of exons 1 and 50, respectively. Other 7 patients had deletions of exons 48, 51, 52 and 57. Conclusions: Electrocardiogram showed the first changes in pediatric patients with DMD. In cases with dilated cardiomyopathy and arrhythmia, the deletion of exon 52 was detected.