Duchenne Muscular Dystrophy: Clinical Characteristics, Molecular Mechanisms and Management

The dystrophinopathies encompass a range of X-linked muscle disorders varying from mild to severe, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and DMD-associated dilated cardiomyopathy (DCM). DMD typically manifests in early childhood and progresses rapidly, with affected children becoming wheelchair-dependent by the age of 12. Increased serum CK levels are detected in almost all DMD patients. Pathogenic variants in the DMD gene affect dystrophin expression, leading to DMD. More than four thousand pathogenic variants have been identified in the DMD gene. deletions of one or more exons are the most common variants in the DMD gene and are found in 60%-70% of patients. With current genetic methods, it is possible to elucidate the molecular etiology in approximately 95% of patients. Penetrance of DMD is complete in males. The penetrance varies in heterozygous carrier females and may depend, partly, X-chromosome inactivation (XCI) patterns. Since DMD has X-linked inheritance pattern, carrier screening should always be considered for mothers of boys with DMD. There are two important points to remember in genetic counseling for DMD. One is that 33% of DMD cases are sporadic (de novo), and the other is that the probability of germline mosaicism for DMD is 15%-20%. Sarcoglycanopathies, Emery-Dreifuss muscular dystrophy, and Barth syndrome are diseases that are included in the differential diagnosis of DMD. Since multiple systems can be affected in DMD patients, management ideally should be provided within a multidisciplinary care setting. Although corticosteroids have been shown to increase muscle strength in DMD patients and are frequently used, they are not a curative treatment. In recent years, antisense oligonucleotides and nonsense suppression therapies have emerged as variant-specific treatments. Also, several new and promising therapies have entered clinical trials or are on the horizon. In this chapter, in addition to this summary about DMD, more comprehensive information is provided.