Duchenne Dystrophy Flashcards
Definition of Duchenne’s muscular dystrophy
Duchenne muscular dystrophy is an X-linked recessive disorder caused by mutations in the DMD gene, which encodes the protein dystrophin.
DMD leads to the progressive degeneration and weakening of muscles, primarily affecting skeletal and cardiac muscles.
It is characterized by muscle weakness, difficulty with motor skills, and eventual loss of ambulation.
Pathomechanism of Duchenne’s muscular dystrophy
The absence or deficiency of dystrophin, a protein crucial for maintaining the structural integrity of muscle cells, is the key pathomechanism in Duchenne muscular dystrophy. Without dystrophin, the muscle fibers are more susceptible to damage during muscle contraction and relaxation.
This results in repeated cycles of muscle fiber degeneration and regeneration, leading to the progressive loss of muscle tissue and replacement by fibrotic (scar) tissue.
Causes of Duchenne’s muscular dystrophy
Duchenne muscular dystrophy is caused by mutations in the DMD gene located on the X chromosome. As a result, males are predominantly affected, while females typically carry the mutation but are usually asymptomatic or may have milder symptoms due to the presence of a normal copy of the gene on their second X chromosome.
The most common mutation in DMD is a large deletion or duplication of one or more exons in the DMD gene, resulting in a non-functional or truncated dystrophin protein.
Symptoms of Duchenne’s muscular dystrophy
The symptoms of Duchenne muscular dystrophy typically manifest in early childhood and progressively worsen over time. Common symptoms include:
Muscle weakness: Initially affecting the muscles of the hips, pelvis, thighs, and shoulders, leading to difficulty with walking, running, and climbing stairs.
Delayed motor milestones: Delays in reaching developmental milestones such as sitting, standing, and walking.
Gower’s sign: Difficulty getting up from the floor, using the hands to walk up the legs (“climbing up the body”) due to weak proximal muscles.
Waddling gait: A characteristic walking pattern with an exaggerated, side-to-side swaying of the hips.
Contractures: The progressive loss of muscle tissue can result in the shortening and tightening of tendons and muscles, leading to joint contractures and limited range of motion.
Cardiomyopathy: Weakening of the heart muscle, leading to cardiac complications such as cardiomyopathy and arrhythmias.
Diagnosis and differential diagnosis of Duchenne’s muscular dystrophy
Clinical evaluation: A thorough physical examination to assess muscle strength, motor milestones, Gower’s sign, and presence of contractures.
Genetic testing: DNA analysis to detect mutations in the DMD gene, either through targeted sequencing or multiplex ligation-dependent probe amplification (MLPA) to identify large deletions or duplications.
Creatine kinase (CK) levels: Blood tests to measure CK levels, which are typically significantly elevated in individuals with DMD due to muscle fiber breakdown.
Muscle biopsy: In some cases, a muscle biopsy may be performed to assess the presence of dystrophin and confirm the diagnosis. However, this is less commonly done now with the availability of genetic testing.
DDx:
Becker muscular dystrophy: A milder form of muscular dystrophy caused by mutations in the same DMD gene but resulting in a partially functional dystrophin protein.
Limb-girdle muscular dystrophy: A group of genetic disorders characterized by weakness and wasting of the muscles in the shoulders and hips.
Spinal muscular atrophy: A genetic disorder characterized by the degeneration of motor neurons in the spinal cord, leading to muscle weakness and atrophy.
Congenital myopathies: A heterogeneous group of genetic muscle disorders characterized by muscle weakness and structural abnormalities.
Treatment of Duchenne’s muscular dystrophy
Corticosteroids: Glucocorticoid medications, such as prednisone or deflazacort, are commonly prescribed to help slow the progression of muscle weakness and delay the loss of ambulation.
Physical therapy: Regular physical therapy and exercises focusing on stretching, strengthening, and maintaining mobility can help manage symptoms and maintain functional abilities.
Assistive devices: The use of mobility aids, orthopedic devices, and adaptive equipment can assist with mobility and activities of daily living.
Cardiac management: Regular cardiac evaluations and appropriate management of cardiomyopathy and arrhythmias are essential.
Respiratory support: As respiratory muscles weaken over time, interventions such as non-invasive ventilation or respiratory assist devices may be required.
Genetic counseling: Genetic counseling is important for affected individuals and their families to understand the inheritance pattern and the risk of passing the condition to future generations.
Complications of Duchenne’s muscular dystrophy
Progressive muscle weakness: Muscles continue to weaken over time, affecting mobility, functional abilities, and independence.
Contractures: Joint contractures and limited range of motion can significantly impact mobility and activities of daily living.
Cardiac complications: Cardiomyopathy and arrhythmias can lead to heart failure and other cardiac-related complications.
Respiratory difficulties: Progressive weakness of respiratory muscles can result in respiratory insufficiency and the need for respiratory support.
Spinal deformities: Scoliosis and other spinal deformities may develop as the disease progresses.
