Myopathies and Muscular Dystrophy: An Overview
Introduction
Myopathies are primary disorders of muscles that manifest as pathological, biochemical, or electrical abnormalities. These conditions are typically characterized by:
- Proximal muscle group involvement
- Muscle wasting
- Absence of reflexes
- Fibrillation
- Bilateral involvement
- Normal central and peripheral nervous systems
- Progressive downhill course without remission
Some myopathies are genetically determined and may have hereditary transmission, though their exact causes remain elusive.
Muscular dystrophies represent a heterogeneous group of inherited disorders marked by gradual muscle fiber degeneration. Key features include:
- Onset in early life
- Proximal muscle involvement
- Loss of deep tendon reflexes
- Pseudohypertrophy of muscles
Muscular dystrophy is distinct from other muscle diseases based on four mandatory criteria:
- It is a primary myopathy.
- There is a genetic basis for the disorder.
- The course is progressive.
- Muscle fiber degeneration and death occur at some stage of the disease.
In muscular dystrophy, muscle wasting and weakness are symmetrical, tendon reflexes are preserved until late stages, and there is no sensory loss. The severity and progression vary significantly between types, from severe forms present at birth to slow-progressing types spanning decades.
Classification of Muscular Dystrophies
| X-linked Recessive | Autosomal Recessive | Autosomal Dominant |
| Duchenne | Limb-girdle type | Facioscapulohumeral |
| Becker | Childhood type | Emery-Dreifuss |
| McLeod’s type | Congenital muscular dystrophy | Oculopharyngeal |
Duchenne Muscular Dystrophy (DMD)
Duchenne muscular dystrophy (DMD) is the most common, extensively studied, and severe form of muscular dystrophy. It predominantly affects males, with females serving as carriers.
Pathophysiology
DMD is an X-linked recessive genetic disorder caused by a deletion in the DMD gene located on the X-chromosome (cytogenetic band Xp21). This gene codes for dystrophin, a protein essential for muscle membrane stabilization during contractions. The absence of dystrophin leads to muscle fiber fragility, membrane leakage, and subsequent muscular dystrophy.
Key statistics:
- Incidence: 1 in 3,500 live male births
- High mutation rate: One-third of new cases arise without a prior family history
- Dystrophin levels correlate inversely with disease severity
Clinical Features
Children with DMD typically exhibit muscle weakness by five years of age. Common early signs include:
- Difficulty climbing stairs
- Frequent falls
- Delayed motor milestones
- Inability to run
Other characteristic features:
- Onset: Between 3-6 years
- Progressive weakness: Symmetrical and proximal
- Pseudohypertrophy: Calf muscles and occasionally quadriceps
- Spinal deformities: Lordosis and scoliosis
- Gowers’ sign: A compensatory maneuver to rise from the floor due to pelvic muscle weakness
- Cardiopulmonary involvement: Mild to moderate mental retardation
The disease progression is predictable, transitioning through:
- Ambulatory stage (up to 7 years): The child can walk.
- Wheelchair-dependent stage (up to 12 years): Mobility declines.
- Bedbound stage (up to 19-20 years): Complete loss of mobility.
Death usually occurs in the third decade due to respiratory infections or cardiomyopathy.
Stages of DMD
| Stage | Functional Ability |
| Stage I | Fully ambulatory |
| Stage II | Climbs stairs with support |
| Stage III | Can stand from sitting with assistance |
| Stage IV | Walks with support |
| Stage V | Wheelchair independent |
| Stage VI | Wheelchair dependent |
| Stage VII | Confined to bed (independent) |
| Stage VIII | Confined to bed (dependent for all ADLs) |
Complications
1. Respiratory
- Recurrent infections
- Restrictive pulmonary disease
- Chronic alveolar hypoventilation
- Cor pulmonale and ventricular failure
2. Cardiomyopathy
- Progressive heart muscle dysfunction affects both patients and carriers.
3. Scoliosis
- Develops during the ambulatory stage and worsens after wheelchair dependence, significantly impairing respiratory function.
4. Contractures
- Early contractures in the lower limbs affect mobility, while upper limb contractures result from prolonged wheelchair use.
Investigations
- Serum muscle enzymes:
- Creatine phosphokinase (CPK) levels are elevated (>10 times normal).
- Other enzymes like pyruvate kinase and lactate dehydrogenase may also be elevated.
- Electromyography (EMG):
- Detects denervated potentials in skeletal muscles.
- Muscle biopsy:
- Reveals muscle degeneration and regeneration.
- Cardiac evaluation:
- ECG and echocardiograms assess cardiac function.
- Genetic counseling:
- Essential for family planning and carrier detection.
Rehabilitation
Ambulatory Stage
- Early detection and prevention of contractures through passive stretching, prone lying, and splinting.
- Physical therapy for endurance and respiratory muscle strengthening.
- Psychological support for the patient and family.
Wheelchair-Dependent Stage
- Respiratory management, including breathing exercises and assisted ventilation.
- Training in activities of daily living (ADL) using assistive devices.
- Prevention of scoliosis through wheelchair modifications.
Prolonged Survival Stage
- Use of non-invasive respiratory aids.
- ADL facilitation using communication aids like personal computers with voice synthesizers.
Conclusion
Duchenne muscular dystrophy is a devastating condition with profound physical, emotional, and psychological impacts. Early diagnosis, consistent rehabilitation, and psychological support can improve the quality of life for affected individuals and their families. Although there is no cure, advancements in genetic and supportive therapies offer hope for better management and prolonged survival. Improving awareness and providing comprehensive care remain critical in addressing the challenges of this condition.
