Overview
Definition:
Duchenne muscular dystrophy (DMD) is a severe, inherited X-linked recessive neuromuscular disorder characterized by progressive muscle degeneration and weakness
It is caused by mutations in the DMD gene, leading to a deficiency of the dystrophin protein, which is crucial for muscle fiber integrity
Steroid therapy, primarily with corticosteroids, is a cornerstone in managing DMD to slow disease progression and improve quality of life.
Epidemiology:
DMD is one of the most common childhood-onset muscular dystrophies, affecting approximately 1 in 3,500 to 5,000 live male births worldwide
It is significantly more prevalent in males due to its X-linked inheritance pattern
Carrier females are usually asymptomatic but can exhibit mild muscle weakness.
Clinical Significance:
DMD leads to profound disability, affecting ambulation, respiration, and cardiac function, significantly impacting survival
Early and appropriate management, including steroid therapy, is critical to delaying functional decline, improving muscle strength, and prolonging survival
Understanding steroid efficacy, side effects, and optimal regimens is paramount for pediatricians and neurologists preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Delayed motor milestones in infancy and early childhood
Proximal muscle weakness evident by 2-3 years of age
Waddling gait
Frequent falls
Difficulty rising from a seated position (Gower's sign)
Calf pseudohypertrophy
Loss of ambulation typically occurs between ages 7-12 years
Later, skeletal deformities, respiratory compromise, and cardiomyopathy develop.
Signs:
Gower's sign: using hands to push off the thighs to stand
Waddling gait
Lumbar lordosis
Calf pseudohypertrophy (enlarged, firm calf muscles due to fatty infiltration)
Reduced range of motion in hips and knees
Muscle wasting, particularly in the thighs and shoulders
Presence of scoliosis or kyphosis as the disease progresses.
Diagnostic Criteria:
Diagnosis is typically suspected based on clinical presentation and confirmed by elevated serum creatine kinase (CK) levels, which are markedly elevated (hundreds to thousands of times normal)
Genetic testing to identify mutations in the DMD gene is the gold standard
Muscle biopsy showing absence or severe reduction of dystrophin protein on immunostaining can also be diagnostic.
Diagnostic Approach
History Taking:
Detailed birth and developmental history focusing on motor milestones
Family history of neuromuscular disorders, particularly muscular dystrophies or unexplained muscle weakness in males
Onset and progression of symptoms
Specific difficulties encountered by the child (e.g., climbing stairs, running, jumping)
History of cardiac or respiratory issues.
Physical Examination:
Assess muscle strength globally and specifically in proximal and distal muscle groups
Evaluate gait and posture
Perform Gower's sign assessment
Check for calf pseudohypertrophy
Assess for scoliosis, contractures, and joint range of motion
Auscultate heart and lungs for evidence of cardiomyopathy or respiratory compromise.
Investigations:
Serum creatine kinase (CK) levels: Markedly elevated, often >10 times the upper limit of normal
Genetic testing: Detects deletions, duplications, or point mutations in the DMD gene
essential for definitive diagnosis and carrier testing
Electromyography (EMG) and nerve conduction studies (NCS): May show myopathic changes but are not specific for DMD
Muscle biopsy: Demonstrates absence or severe deficiency of dystrophin protein
useful if genetic testing is inconclusive or for subtyping dystrophinopathies
Electrocardiogram (ECG) and Echocardiogram: To assess for cardiomyopathy, which is common in DMD.
Differential Diagnosis:
Other muscular dystrophies (e.g., Becker muscular dystrophy, limb-girdle muscular dystrophies), congenital myopathies, spinal muscular atrophy (SMA), myotonic dystrophy, inflammatory myopathies, metabolic myopathies, and inflammatory conditions like Guillain-Barré syndrome
Differentiating based on inheritance pattern, age of onset, rate of progression, specific muscle groups affected, and CK levels is crucial.
Management
Initial Management:
Establishing a definitive diagnosis through genetic testing and/or muscle biopsy
Comprehensive baseline assessment including pulmonary function tests, cardiac evaluation (ECG, echocardiogram), and orthopedic assessment
Initiation of corticosteroid therapy.
Medical Management:
Corticosteroids are the mainstay of medical management
Prednisone (0.75 mg/kg/day) or Deflazacort (0.9 mg/kg/day) are commonly prescribed
They are shown to improve muscle strength, slow progression of muscle weakness, preserve ambulation for longer, and improve pulmonary function
Treatment is typically initiated between ages 5-6 years, or earlier if ambulation is declining
Continuous vs
intermittent dosing strategies exist, with continuous daily dosing generally preferred for maximal benefit
Long-term steroid use necessitates monitoring for side effects.
Surgical Management:
Surgical interventions are mainly supportive and address complications
These include spinal fusion for progressive scoliosis to improve posture, seating, and respiratory function
Achilles tendon lengthening to improve gait or facilitate brace fitting
Tracheostomy or ventilatory support in advanced respiratory failure
Gastrostomy tube placement for nutritional support if dysphagia develops.
Supportive Care:
Physical therapy: To maintain range of motion, prevent contractures, and maximize functional mobility
Occupational therapy: To assist with adaptive equipment and daily living activities
Respiratory care: Regular monitoring of pulmonary function, respiratory muscle strength, and consideration of non-invasive ventilation (NIV) or invasive ventilation as disease progresses
Cardiac care: Regular cardiac monitoring and management of heart failure with appropriate medications
Nutritional support: Ensuring adequate caloric intake and managing potential constipation or gastroesophageal reflux
Psychological and social support for the patient and family.
Steroid Specifics And Monitoring
Indications For Steroids:
Typically initiated between ages 5-6 years, or earlier if there is a decline in ambulation or pulmonary function
Decision should be individualized based on disease progression and patient factors
Steroids are not curative but are disease-modifying.
Drug Options And Dosing:
Prednisone: 0.75 mg/kg/day orally
Deflazacort: 0.9 mg/kg/day orally
Both have demonstrated efficacy in slowing DMD progression
Deflazacort may have a slightly better bone tolerance profile compared to prednisone, but both carry risks of fracture
Dosing is usually given as a single morning dose
Alternate day or intermittent dosing may be used in specific situations but is generally less effective.
Monitoring For Side Effects:
Weight gain, increased appetite, behavioral changes (irritability, mood swings), hirsutism, acne
Osteoporosis and fractures (calcium and vitamin D supplementation, regular bone density monitoring)
Growth retardation
Cataracts and glaucoma
Cushingoid features
Hyperglycemia and diabetes mellitus
Hypertension
Increased susceptibility to infections
Gastric irritation or peptic ulcer disease
Monitor growth, bone mineral density, vision, glucose levels, blood pressure, and general well-being.
Complications
Early Complications:
Increased susceptibility to infections due to immunosuppression
Acute exacerbations of muscle weakness during intercurrent illnesses
Behavioral disturbances related to steroid initiation
Gastrointestinal upset.
Late Complications:
Osteoporosis and pathological fractures
Scoliosis and kyphosis, leading to restrictive lung disease
Cardiomyopathy and heart failure
Respiratory failure and sleep-disordered breathing
Obesity
Cataracts
Growth retardation
Diabetes mellitus.
Prevention Strategies:
Prophylactic calcium and vitamin D supplementation
Regular monitoring of bone mineral density
Early identification and management of scoliosis through bracing and surgical intervention if necessary
Regular cardiac and pulmonary function assessments
Close monitoring of glucose and blood pressure
Judicious use of steroids, balancing benefits against risks
Prompt treatment of infections.
Prognosis
Factors Affecting Prognosis:
Age of onset of symptoms
Rate of disease progression
Onset of cardiac involvement
Development of significant scoliosis
Response to corticosteroid therapy
Maintenance of ambulation
Respiratory function.
Outcomes:
With optimal management including corticosteroids, lifespan has significantly increased, with many individuals living into their late 20s or 30s, and some longer
Steroids help preserve ambulation for longer, improve muscle strength, and delay the onset of severe respiratory and cardiac complications
However, DMD remains a fatal disease.
Follow Up:
Regular multidisciplinary follow-up is essential, typically every 3-6 months
This includes assessments by pediatric neurologists, pulmonologists, cardiologists, orthopedic surgeons, physical and occupational therapists, and dietitians
Ongoing monitoring for disease progression and steroid-related side effects is critical.
Key Points
Exam Focus:
Key differential diagnoses for muscle weakness in children
Indications and contraindications for steroid therapy in DMD
Specific corticosteroid agents (prednisone, deflazacort) and their typical dosages
Major side effects of long-term corticosteroid use and their management
Management of common complications like scoliosis and cardiomyopathy
Understanding the role of genetic testing and CK levels in diagnosis
Typical age of loss of ambulation.
Clinical Pearls:
Always consider Gower's sign as a pathognomonic finding for proximal muscle weakness
Calf pseudohypertrophy is a key physical exam finding
Initiate steroid therapy proactively to maximize benefit before significant functional decline
Monitor steroid side effects vigilantly and implement preventive strategies
A multidisciplinary approach is crucial for comprehensive care
Educate families about the disease trajectory and management goals.
Common Mistakes:
Delaying steroid initiation until significant ambulation loss occurs
Underestimating the importance of monitoring for and managing steroid side effects
Failing to adequately screen for and manage cardiac and respiratory complications
Not involving a multidisciplinary team early in the management process
Misinterpreting symptoms of steroid toxicity as disease progression.