A Mini-Review on The Rehabilitation of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy, a rare X-linked disorder, is caused by a genetic mutation that prevents the body from producing dystrophin [1], a protein that enables muscles to work properly. It is one of the most common types of muscular dystrophy. DMD symptom onset is in early childhood, usually between ages 3 and 5 years. Over time, children with Duchenne will have difficulty walking and breathing, then lead to disability, dependence, and premature death. The disease primarily affects boys, but in rare cases, it also can affect girls. The prevalence of DMD is approximately 1 in 3500 to 5000 male births worldwide [2]. Muscle weakness is the principal symptom of DMD and worsens over time, first affecting the proximal muscles and later affecting the distal limb muscles. Patients with DMD progressively lose the ability to perform activities independently and often require a wheelchair by their early teens. As the disease progresses, life-threatening heart and respiratory conditions can occur [3]. In general, patients succumb to the disease in their 20s or 30s [3]; however, disease severity and life expectancy can vary.
DMD is caused by mutations in the DMD gene, which encodes the protein product called dystrophin. DMD gene is one of the largest of the identified human genes, spanning 2.4 Mb of a genomic sequence and corresponding to about 0.1% of the total human genome [4]. The gene consists of 79 exons encoding a 14,000 bp messenger RNA transcript that is translated into dystrophin [5]. The most common mutation responsible for DMD is a deletion spanning one or multiple exons. Such deletions account for 60-70% of all DMD cases. Point mutations are responsible for around 26% of DMD cases. Exonic duplications account for 10 to 15% of all DMD cases [6]. Mutations in the DMD gene disrupt the protein’s reading frame causing premature stop codons, leaving little or no functional dystrophin protein produced in cells.
Despite major therapeutic advances over the past 30 years, there are currently no curative therapies for DMD. Gene therapy is a promising experimental method that uses genes (the fundamental units of heredity) to treat disorders that result from genetic mutations. Currently, several kinds of gene-based therapies including exon skipping are being developed to treat DMD. Rehabilitation plays a critical role in overall management for individuals with DMD. The rehabilitation team can include physicians, Physical Therapists (PTs), Occupational Therapists (OTs), Speech and Language Therapists (SALTs), dieticians, orthotists, and durable medical equipment providers. Rehabilitation management requires an understanding of DMD pathology, natural history, and disease progression; providers should consider each individual’s goals and lifestyle to optimize quality of life across the lifespan [7-9]. Rehabilitation can be provided in outpatient and school settings and should continue throughout the patient’s life. The patient should be assessed by a rehabilitation specialist at least every 6 months or more frequently if concerns [10,11].
International guidelines for DMD care were initially published in 2010 [12,13], with recommendations for DMD management, assessment, and intervention. However, because of significant advances in the understanding and management of DMD since then, DMD care considerations were recently updated to address the evolving needs of DMD patients [7-9]. The new DMD care considerations represent a fundamental shift in the care of people with DMD. Although in the past the main goal of DMD care was the prolongation of survival, the focus has changed to optimization of the quality of life, psychosocial management, independence, and transition to adulthood. The guidelines continue to highlight the importance of rehabilitation for Duchenne patients. Recommendations include daily preventive home stretching programs and select orthotic interventions, splinting, casting, positioning, and equipment. Submaximal aerobic activity (e.g., swimming and cycling) and avoidance of eccentric and high-resistance exercise are also recommended [11-13]. Figure 1 includes an overall summary of rehabilitative care across all disease stages of DMD. Adapted from Laura E et al. [7-9,14].

Figure 1:

Rehabilitation plays a critical role to overall management for individuals with DMD. Lifelong rehabilitation is paramount in assisting people with DMD to reach their full potential.

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