Muscular dystrophies

Question 1

How are muscular dystrophies classified?

Answer 1

According to the inheritance pattern, clinical pattern of muscles involved and the genes responsible.

Question 2

What types of mutations cause severe muscular dystrophy?

Answer 2

Ones resulting in frame shift.

Question 3

What types of mutations cause moderate to severe muscular dystrophy?

Answer 3

Ones resulting in altered binding.

Question 4

What types of mutations cause mild muscular dystrophy?

Answer 4

Mutations in the middle rod e.g. Becker.

Question 5

What pathological features do we see in muscular dystrophy?

Answer 5

Prolonged destruction of single fibres, regeneration and fibrosis/scarring in the muscle.

Question 6

When does duchenne muscular dystrophy commonly present?

Answer 6

2-4 years of age although some come on later.

Question 7

What age do DMD sufferers normally survive to?

Answer 7

Usually die by the age of 20.

Question 8

What serum results do we usually see in DMD?

Answer 8

Raised CK.

Question 9

What does DMD cause?

Answer 9

Proximal weakness, pseudo hypertrophy of calves. (Look big but actually weak).

Question 10

What mutation causes DMD?

Answer 10

Mutations in dystrophin gene on long arm of chromosome X.

Question 11

What does the dystrophin mutation cause in tissues of DMD sufferers?

Answer 11

Alterations in anchorage of actin cytoskeleton to basement membrane. Means that fibres are liable to tear which causes Ca2+ release triggering the apoptopic pathway. Causes uncontrolled calcium entry into cells.

Question 12

What histological features do we see in DMD?

Answer 12

Muscle fibre necrosis and phagocytosis, regeneration, chronic inflammation and fibrosis and hypertrophy.

Question 13

What causes BMD (Becker) and how does it differ/is similar with DMD?

Answer 13

Mutation in dystrophin (same as DMD but a different mutation)
Becker has later onset and slower progression.
Both affect type 1 and 2 fibres and cause high CK.

Question 14

What signs and symptoms does myotonic dystrophy show?

Answer 14

Muscle weakness, myotonia and non muscle features e.g. Cataracts, frontal baldness in men, cardiomyopathy and low intelligence.

Question 15

What kind of mutation causes myotonic dystrophy?

Answer 15

An autosomal dominant mutation.

Question 16

What muscles does myotonic dystrophy initially effect?

What are muscles latterly affected?

Answer 16

Face and distal limbs, moving on to respiratory muscles later.

Question 17

What histological features are seen in myotonic dystrophy?

Answer 17

Atrophy of type 1 muscles, central nuclei, ring fibres, fibre necrosis and fibrofatty replacement.

Question 18

What features do we see in histological samples of muscle fibres in muscular dystrophy sufferers?

Answer 18

Variability in muscle fibres size.
Endomysial fibrosis.
Fatty infiltration and replacement
Myocyte hypertrophy and fibre splitting
Increased central nuclei
Segmental necrosis
Regeneration
Ring fibres