Abstract
X-linked dilated cardiomyopathy (XLDCM) is a distinct phenotype of dystrophinopathy characterized by preferential cardiac involvement without any overt skeletal myopathy. XLDCM is caused by mutations of the Duchenne muscular dystrophy (DMD) gene and results in lethal heart failure in individuals between 10 and 20 years. Patients with Becker muscular dystrophy, an allelic disorder, have a milder phenotype of skeletal muscle involvement compared to Duchenne muscular dystrophy (DMD) and sometimes present with dilated cardiomyopathy. The precise relationship between mutations in the DMD gene and cardiomyopathy remain unclear. However, some hypothetical mechanisms are being considered to be associated with the presence of some several dystrophin isoforms, certain reported mutations, and an unknown dystrophin-related pathophysiological mechanism. Recent therapy for Duchenne muscular dystrophy, the severe dystrophinopathy phenotype, appears promising, but the presence of XLDCM highlights the importance of focusing on cardiomyopathy while elucidating the pathomechanism and developing treatment.
Highlights
Dystrophinopathy is an X-linked disorder caused by mutations in the Duchenne muscular dystrophy (DMD) gene encoding for the sarcolemmal protein dystrophin
Muntoni et al reported an X-linked dilated cardiomyopathy (XLDCM) family having a deletion mutation spanning from a muscle promoter to a portion of intron 1 in the DMD gene
Based on the previous case reports, the DMD gene mutations occurring with XLDCM or mild Becker muscular dystrophy (BMD)
Summary
Dystrophinopathy is an X-linked disorder caused by mutations in the DMD gene encoding for the sarcolemmal protein dystrophin. BMD shows a milder phenotype of skeletal muscle involvement than DMD and patients can generally walk beyond 16 years of age, its severity or course varies among patients. The gene encodes the 427 kDa cytoskeletal protein dystrophin which is a rod-shaped structure consisting of four domains including an N-terminal actin-binding domain (Figure 1B). If the reading-frame is maintained despite the presence of a mutation (in-frame), a truncated but functional dystrophin is expressed, leading to the BMD phenotype [8]. Some cases present primarily with cardiac manifestations with mild or slight skeletal muscle involvement [10,11,12,13,14,15,16]. X-linked dilated cardiomyopathy (XLDCM), a distinct cardio-specific phenotype of dystrophinopathy, is described in the paragraph
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