Muscular Dystrophies

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Muscular dystrophies are a group of inherited neuromuscular disorders characterised by progressive muscle weakness and degeneration due to defects in muscle proteins.

Aetiology

Muscular dystrophies are caused by genetic mutations affecting proteins necessary for muscle structure and function. Common types include:

1. Duchenne Muscular Dystrophy (DMD):

  • X-linked recessive disorder affecting the dystrophin gene.
  • Severe form, symptoms begin in early childhood.

2. Becker Muscular Dystrophy (BMD):

  • Milder form of DMD with later onset.
  • Caused by partially functional dystrophin.

3. Myotonic Dystrophy:

  • Autosomal dominant disorder affecting muscle relaxation.
  • Progressive muscle wasting, myotonia (delayed muscle relaxation).

4. Limb-Girdle Muscular Dystrophy (LGMD):

  • Weakness in shoulder and hip muscles.
  • Both autosomal recessive and dominant forms exist.

5. Facioscapulohumeral Muscular Dystrophy (FSHD):

  • Weakness in face, shoulders, upper arms.
  • Autosomal dominant inheritance.

Pathophysiology

  • Mutations in genes encoding muscle proteins (e.g., dystrophin in DMD/BMD).
  • Loss of structural integrity leads to muscle fibre damage.
  • Progressive muscle degeneration and replacement with fat and fibrosis.
  • Respiratory and cardiac muscles may also be affected in advanced disease.

Risk factors

  • Family history of muscular dystrophy.
  • Male sex (DMD and BMD are X-linked).
  • Genetic predisposition (autosomal dominant or recessive inheritance in some types).

Signs and symptoms

General Symptoms:

  • Progressive muscle weakness and wasting.
  • Difficulty with walking, climbing stairs.
  • Frequent falls, waddling gait.
  • Gower’s sign (child uses hands to "climb up" legs when rising from the floor).

Specific Symptoms by Type:

Duchenne Muscular Dystrophy (DMD):
  • Onset in early childhood (before 5 years).
  • Delayed motor milestones.
  • Pseudohypertrophy (enlarged calf muscles due to fat deposition).
  • Cardiomyopathy and respiratory failure in later stages.
Becker Muscular Dystrophy (BMD):
  • Similar to DMD but later onset and slower progression.
  • May have normal lifespan.
Myotonic Dystrophy:
  • Difficulty relaxing muscles (myotonia).
  • Cataracts, cardiac arrhythmias.
  • Frontal balding, testicular atrophy.

Investigations

  • Creatine kinase (CK): elevated in muscle breakdown (markedly high in DMD).
  • Genetic testing: identifies mutations in dystrophin or other genes.
  • Muscle biopsy: shows muscle degeneration and fibrosis.
  • Electromyography (EMG): distinguishes between neurogenic and myopathic disease.
  • Cardiac assessment: ECG and echocardiogram for cardiomyopathy (especially in DMD/BMD).
  • Pulmonary function tests: assess respiratory involvement.

Management

1. Supportive and Symptomatic Treatment:

  • Physiotherapy: prevent contractures, maintain mobility.
  • Orthopaedic support: braces, wheelchair use in later stages.
  • Respiratory support: non invasive ventilation for respiratory failure.
  • Speech and swallowing therapy: if bulbar involvement present.

2. Pharmacological Treatment:

Duchenne and Becker Muscular Dystrophy:
  • Corticosteroids (prednisolone, deflazacort): slow disease progression.
  • ACE inhibitors or beta blockers: for cardiomyopathy.
Myotonic Dystrophy:
  • Mexiletine: for myotonia.
  • Pacemaker: if cardiac conduction defects present.

3. Emerging and Genetic Therapies:

  • Gene therapy: experimental trials targeting dystrophin mutations.
  • Exon-skipping drugs (e.g., eteplirsen for DMD): increases production of functional dystrophin.
NeurologymypanotesMuscular Dystrophies