Muscular dystrophies Flashcards

1
Q

Definition

A

Group of inherited diseases that cause progressive weakness and loss of muscle mass

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2
Q

Aetiology

A

In all cases, a genetic mutation = underlying cause
- dystrophin gene on X chromosome
- Inherited in X-linked recessive manner.

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3
Q

Types of dystrophinopathy

A

Duchenne muscular dystrophy (DMD)
- Frameshift or nonsense mutations result in no dystophin protein
- More severe Sx
- Presents from age 2-3

Becker muscular dystrophy (BMD):
- Missense mutations results in misshapen dystrophin protein
- Milder presentation
- Presents from age 10-20

DMD-associated dilated cardiomyopathy
- Similar pathophysiology
- Cardiac muscle involvement only

Myotonic dystrophy
Facioscapulohumeral dystrophy .

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4
Q

Epidemiology

A

Male
FHx

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5
Q

Pathophysiology

A

The dystrophin gene encodes a protein which links intracellular actin to the cytoplasmic dystrophin-associated protein complex .
In the absence of dystrophin, the muscular cell membrane (sarcolemma) becomes unstable and results in the release of creatine kinase and muscle necrosis.
In the short term there is muscle regeneration, however over time the muscle is infiltrated by fat and fibrotic tissue, resulting in weakness. Esp notable in the lower limbs

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6
Q

Signs

A
  • Gower’s sign: child will stand up using their arms to push up due to weakness in lower limbs
  • Muscle wasting
  • Calf pseudohypertrophy: visibly enlarged calves due to fat and fibrotic tissue
  • Waddling gait
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7
Q

Symptoms

A

Muscle weakness:
- Proximal muscles first
- Distal muscles later
- Lower limbs before upper limbs
Delayed ability to sit, stand or walk

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8
Q

Diagnosis

A

Creatine kinase: elevated because muscle necrosis
- a nonspecific test result
Muscle biopsy: immunohistochemical analysis, along with 11 other muscle protein abnormalities
Genetic testing: common mutations in dystrophin

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9
Q

Treatment

A

No cure
- Mobility assistance
- Medical therapies:
= corticosteroids to help improve muscle strength
= ACE-i/BB for cardiomyopathy
- Surgery: postural abnormalities e.g. scoliosis
- Genetic counselling to parents

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10
Q

Complications

A
  • Respiratory failure
  • Inability to walk
  • Dilated cardiomyopathy: most important life-limiting complication in DMD
  • Arrhythmias: dystrophin gene also in heart muscle
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