Muscular Dystrophy
Muscular dystrophy is an umbrella term for a group of inherited muscle disorders causing progressive muscle weakness. This article focuses on Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), the main dystrophinopathies that are most important and most commonly examined at a non-specialist level.
Causes and Pathophysiology
Both DMD and BMD are genetic conditions caused by mutations in the DMD gene (which encodes dystrophin, a cytoskeletal protein important for muscle fibre stability)
- Inheritance pattern: X-linked recessive
- DMD: more severe, as mutations result in absolute deficiency of functional dystrophin
- BMD: less severe, as mutations usually result in a relative deficiency of dystrophin
As DMD and BMD are X-linked recessive conditions, they predominantly affect males.
- Carrier females are usually asymptomatic or mildly affected, but may develop cardiac involvement
- A carrier mother has a 50% chance of passing the mutation to each son, who would be affected, and a 50% chance of passing it to each daughter, who would become a carrier
- An affected father passes the mutation to all daughters, who become carriers, but not to sons
Affected male = mutation is on the X chromosome from the maternal side or from a new mutation (de novo). Not father-to-son transmission.
Clinical Features
DMD features:
| Body system | Clinical features |
|---|---|
| Musculoskeletal | Hallmark: progressive bilateral, symmetrical muscle weakness
Motor signs are typically noticed before 5 y/o
Patients often lose the ability to walk around age 10-12 y/o Increased risk of:
|
| Cardiovascular |
|
| Respiratory | Respiratory muscle weakness causes breathing problems
|
| GI and nutritional |
Obesity can occur due to reduced mobility / steroids; or undernutrition can occur due to dysphagia / feeding difficulty |
| Neurodevelopmental and psychosocial |
|
| Life expectancy | Most individuals now live into their 30s and beyond
Most common cause of death: cardiac or respiratory failure |
BMD presents similarly to DMD but with the following differences:
- BMD is less severe than DMD
- Onset in later childhood (~5-15 y/o)
- Slowly progressive
- Typically do NOT reduce life expectancy
Investigation and Diagnosis
Standard work-up for ALL patients:
- 1st line: serum creatine kinase (↑ creatine kinase is seen in DMD and BMD due to muscle breakdown)
- Confirmatory test: genetic testing to detect mutations in the dystrophin gene (DMD gene)
If genetic testing is -ve and clinical suspicion of DMD / BMD remains → muscle biopsy
- Immunohistochemistry to demonstrate complete absence of dystrophin protein (DMD) or deficiency in dystrophin protein (BMD)
Management
Both DMD and BMD require an MDT management approach.
Duchenne Muscular Dystrophy (DMD)
Mainstay of treatment: glucocorticoids (prednisolone or deflazacort)
- Steroids are disease-modifying as they slow the disease progression
- Steroids also delay loss of walking ability and help preserve upper limb strength and respiratory function
Other aspects of management:
- Daily home stretching programme + use of ankle-foot orthoses to prevent contracture development
- ACE inhibitors should be initiated by 10 y/o even if asymptomatic due to the risk of developing DCM
- Steroids often cause impaired growth, delayed puberty, severe osteoporosis
- Testosterone replacement for males >14 y/o with delayed puberty
- IV bisphosphonates for moderate to severe vertebral and long bone fractures
- GI and nutrition
- A dietitian should manage calorie and fluid intake
- When the patient can no longer maintain adequate nutrition or hydration orally → gastrostomy feeding tube
Ongoing surveillance and monitoring
- ECG and echo – due to the risk of DCM (most important)
- Lung function test (specifically FVC)
- Spinal and MSK monitoring (for scoliosis and contracture detection)
- Bone health assessment (DEXA, assessment of calcium and vitamin D intake, spine X-rays to detect asymptomatic vertebral compression fractures) – risk of osteoporosis and fractures is high due to steroid use
- Routine mental health and quality of life screening at each clinic visit
Depolarising muscle relaxants (e.g. suxamethonium) and inhalation anaesthetics are contraindicated as they can trigger fatal rhabdomyolysis and hyperkalaemia.
Becker Muscular Dystrophy (BMD)
Unlike DMD, corticosteroids are not routinely used as disease-modifying therapy in BMD.
Otherwise, the general management principles are similar to DMD (see above).