Cardiac Phenotype-Genotype Associations in DMD/BMD: A Meta-Analysis and Systematic Review

Cardiac involvement of Duchenne and Becker muscular dystrophies (DMD/BMD) is the most common cause of fatal outcomes. It is still unclear whether some DMD/BMD gene mutations might be predictive of cardiac involvement. In this study, we provide a comprehensive overview on genotypes of cardiac disease in DMD/BMD. We systematically searched the PubMed/Medline, EMBASE and Cochrane electronic databases. Search results were filtered to include only human studies, English language and all dates up to August 2019. We summarized and extensively reviewed all studies that passed the selection criteria and performed a meta-analysis on key genotype parameters of cardiac disease in DMD/BMD. Of 3450 articles scanned, we included 18 studies from 9 regions in the meta-analysis. The pooled studies included 2661 DMD/BMD patients and 1324 DMD/BMD patients with cardiac disease. The most common mutation type was exon deletion, with a pooled frequency of 90% (P < 0.01). In DMD/BMD patients with cardiac dysfunction, a higher frequency of involvement of exons 45 and 46 was found in DMD/BMD patients with cardiac dysfunction. This might be predictive of cardiac involvement in patients with DMD/BMD.