What is Duchenne muscular dystrophy (DMD)?

From the Guidelines

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle weakness and degeneration, primarily affecting boys, caused by mutations in the dystrophin gene located on the X chromosome, which prevents the production of dystrophin protein essential for muscle cell stability. This condition affects approximately 1 in every 5000 live male births worldwide, resulting in a significant impact on the quality of life and mortality of those affected 1. The disease is caused by mutations in the DMD gene, leading to a truncated or non-functioning form of the dystrophin protein, which is essential for muscle fiber integrity and repair 1.

Key Characteristics of DMD

• DMD is an X-linked genetic disorder, meaning it primarily affects males, although female carriers can occasionally exhibit symptoms 1.
• The average age of diagnosis is around 4 years, with symptoms typically beginning between ages 2 and 6, including muscle weakness in the legs and pelvis, difficulty running, jumping, and climbing stairs 1.
• As the disease progresses, it affects all voluntary muscles and eventually impacts cardiac and respiratory muscles, leading to a decline in motor function and eventual loss of ambulation in early teens 1.
• Without treatment, life expectancy is limited to the late teens or early twenties, primarily due to respiratory failure or cardiomyopathy leading to heart failure and arrhythmias 1.

Management and Treatment

• Management includes corticosteroids like prednisone (0.75 mg/kg/day) or deflazacort (0.9 mg/kg/day) to slow disease progression, physical therapy to maintain function, and respiratory support as needed 1.
• Newer treatments, such as exon-skipping therapies (eteplirsen, golodirsen) and gene therapies, offer potential benefits, although they are not curative 1.
• Early diagnosis through genetic testing or muscle biopsy is crucial for implementing treatments that can improve quality of life and extend survival, with many patients now living into their 30s or 40s with comprehensive care 1.

Recent Advances and Recommendations

• Recent studies have highlighted the importance of cardiac care in DMD, including the use of cardiac magnetic resonance imaging (CMR) for surveillance of myocardial damage and function, and the consideration of heart failure therapies and non-pharmacological interventions like heart transplantation, mechanical circulatory support, and implantable cardioverter-defibrillators (ICDs) 1.
• The development of respiratory care guidelines for DMD has also been emphasized, with a focus on early intervention and comprehensive management to improve outcomes 1.

From the Research

Definition and Characteristics of Duchenne Muscular Dystrophy (DMD)

• Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder that causes debilitating muscle weakness and atrophy due to a loss of the dystrophin protein 2.
• DMD is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein, leading to degeneration of skeletal and cardiac muscle 3.
• It is a lethal progressive pediatric muscle disorder, genetically inherited as an X-linked disease, caused by mutations in the dystrophin gene 4.

Symptoms and Diagnosis

• Patients with DMD are commonly diagnosed at about 3-5 years of age and progressively decline until complications of the disease often result in death at about 20 years of age 2.
• DMD leads to progressive muscle weakness, degeneration, and wasting, finally resulting in premature demise in affected individuals due to respiratory and/or cardiac failure typically by age 30 4.
• The molecular diagnostic of DMD involves deletions/duplications analysis performed by quantitative techniques such as microarray-based comparative genomic hybridization (array-CGH) and Multiple Ligation Probe Assay (MLPA) 3.

Treatment Options

• While there is no current cure for DMD, several treatment options focus on improving the quality of life and slowing the progression of symptoms associated with the disease 2.
• The current treatment for DMD includes glucocorticoids and physical therapy, as well as respiratory therapy, cardiac management, bone health maintenance, orthopedic interventions, and dietary considerations 2.
• Emerging therapeutic approaches include gene transfer therapy using adeno-associated virus (AAV) vectors and exon skipping agents, which have been shown to be relatively safe with few significant side effects 2.
• Corticosteroid medication therapy is an integral tool for the management of DMD, and several therapeutic options have been recently approved for use 5.