Muscular dystrophy (MD) refers to a group of genetic disorders that cause progressive muscle weakness and loss of muscle mass. The term “Type 2” overwhelmingly refers to Duchenne Muscular Dystrophy (DMD), which is the most common and severe form, affecting approximately one in every 3,500 to 5,000 male births worldwide. DMD is characterized by the rapid, progressive deterioration of voluntary muscles, leading to significant disability. Becker Muscular Dystrophy (BMD) is a milder variant caused by a mutation in the same gene, sometimes grouped with DMD as a dystrophinopathy. Clinical care and research primarily focus on managing DMD due to its profound impact on health and lifespan.
The Underlying Genetic Cause
Duchenne Muscular Dystrophy is classified as an X-linked recessive disorder because the causative DMD gene is located on the X chromosome. Males, who possess only one X chromosome, are predominantly affected, while females typically function as asymptomatic carriers. The DMD gene is the largest known human gene and contains the instructions for creating the Dystrophin protein.
Dystrophin is normally positioned within the muscle fiber, acting as a stabilizing element that connects the muscle’s internal structure to the outer cell membrane. This protein serves a protective function, preventing damage when muscle fibers contract and relax during movement. In DMD, the genetic mutation (often a large deletion or duplication) results in a “frameshift” error that prevents the body from producing any functional Dystrophin protein.
The complete absence of Dystrophin destabilizes the muscle cell membrane, making it highly susceptible to damage during normal activity. This damage triggers the entry of excess calcium, which is toxic to the cell, leading to the death of the muscle fiber. Over time, healthy muscle tissue is progressively replaced by fibrotic scar tissue and fat, which is the hallmark of the disease. In contrast, the milder form, BMD, occurs when the mutation allows for the production of a truncated, partially functional Dystrophin protein, which protects the muscle from rapid degeneration.
Signs, Progression, and Diagnosis
The first signs of DMD typically appear in early childhood, between the ages of two and five, often presenting as developmental delays in motor skills. Parents may notice difficulty running, jumping, or climbing stairs, frequent falling, and an unusual, waddling gait. Another common finding is pseudohypertrophy, the enlargement of the calf muscles, which occurs because muscle tissue is replaced by fat and connective tissue.
A specific manifestation of muscle weakness is Gowers’ sign, where the child must use their hands to “walk” up their own legs to rise from a sitting or squatting position. Weakness follows a predictable pattern, beginning in the proximal muscles (those closest to the body’s center, such as the hips and shoulders) before spreading to the arms and other parts of the body. Most individuals lose the ability to walk unassisted by the age of 12, after which the respiratory and cardiac muscles become increasingly involved.
Diagnosis often begins with a blood test measuring Creatine Kinase (CK), an enzyme that leaks into the bloodstream when muscle is damaged. Individuals with DMD show CK levels elevated 10 to 20 times the upper limit of normal, often before symptoms are noticeable. Definitive diagnosis is confirmed through genetic testing, which analyzes the DNA to pinpoint the specific mutation or deletion within the DMD gene. This analysis is crucial for diagnosis and for determining eligibility for mutation-specific treatments.
Medical and Pharmacological Treatments
The current standard of care involves pharmacological interventions aimed at slowing muscle degeneration and preserving function. Corticosteroids (such as prednisone and deflazacort) are commonly prescribed because they reduce muscle inflammation and slow the decline in strength, delaying the loss of ambulation by several years. A newer synthetic steroid, Vamorolone, has also been approved, offering a potentially more favorable side-effect profile compared to traditional corticosteroids.
Targeted therapies include exon-skipping drugs, which are designed to address certain mutations in the DMD gene. These drugs (including eteplirsen, golodirsen, and casimersen) utilize antisense oligonucleotides to act as a “molecular patch.” The goal is to skip over the mutated section (exon) of the gene’s messenger RNA, correcting the reading frame and allowing the muscle cell to produce a truncated, partially functional Dystrophin protein. This strategy is intended to convert the severe DMD phenotype into the milder BMD form of the disease.
Eligibility for exon-skipping treatments depends entirely on the patient’s specific genetic mutation, making them applicable only to a subset of the DMD population. Beyond these approved treatments, clinical trials are exploring advanced options like gene therapy, where a micro-dystrophin gene is delivered to muscle cells using a viral vector to address the root cause of the disease.
Essential Supportive Care
Managing DMD requires a comprehensive, multidisciplinary approach focused on maintaining function and quality of life beyond medication. Physical therapy (PT) is necessary to maintain a range of motion in the joints and prevent contractures (the painful shortening and stiffening of muscles and tendons). Occupational therapy (OT) helps individuals adapt daily living activities and utilize specialized equipment to maximize independence as muscle weakness progresses.
Continuous monitoring of the heart and lungs is an important element of care, as the heart muscle (cardiomyopathy) and respiratory muscles weaken over time. Respiratory management often includes regular pulmonary function testing and the use of non-invasive ventilation, such as a BiPAP machine, initially during sleep to address nocturnal hypoventilation.
Respiratory Support
As the cough reflex becomes ineffective due to muscle weakness, devices like mechanical insufflators-exsufflators (cough assist devices) are used to help clear secretions. This prevents serious respiratory infections like pneumonia, which is a leading cause of complications.
Nutritional and Mobility Support
Nutritional support is addressed to manage weight and prevent constipation, which can further impact respiratory function. Mobility aids such as braces and wheelchairs are introduced as needed to support ambulation and daily activities.