Muscle disorders- the muscular dystrophies

Duchenne muscular dystrophy
1. epidemiology
  1. commonest phenotype
  2. 1 in 4000 male infants affected
2. aetiology
  1. X-linked recessive inheritance
  2. some have new mutations
  3. deletion on Xp21
    1. codes for dystrophin protein
      1. connects cytoskeleton of a muscle fibre to surrounding extracellular matrix via cell mb
        if deficient -> fibre necrosis (through abnormal intracellular signalling pathways causing)
        Ca2+ ion influx
        breakdown of Ca2+ calmodulin complex
        excess of free radicals
3. Diagnosis
  1. serum creatine phosphokinase (CPK)
    1. sig raised
    2. neonatal screening by this method
      1. in some countries only e.g. Wales
4. presentation
  1. waddling gait &/or lang delay
    1. have to mount stairs 1 by 1
  2. av age of diag= 5.5 years
    1. but often symptomatic much earlier
  3. Gower's sign
    1. need to turn prone to rise
  4. pseudohypertrophy of calves
    1. replacement of mm by fat & fibrous tissue
  5. boys slower & clumsier than peers in early school years
    1. progressive mm atrophy & weakness-> non ambulant by 10-14 years old
  6. episodes of nocturnal hypoxia
    1. secondary to intercostal mm weakness
5. life expectancy reduced to late 20s cos
  1. resp failure
  2. assoc cardiomyopathy
6. 1/3rd of kids have LD
7. complications
  1. scoliosis
8. Mx
  1. approp exercise
    1. maintain muscle power & mobility
    2. delays onset of scoliosis
  2. passive stretching & provision of night splints
    1. prevent contractures esp @ the ankles
  3. orthoses esp those allowing ambulation by leaning from side to side
    1. prolong walking
  4. lengthening Achilles tendon
    1. to aid ambulation
  5. maintaining good sitting posture
    1. reduce risk of scoliosis
  6. scoliosis
    1. truncal brace
    2. moulded seat
    3. ultimately surgical incision of a metal spinal rod
  7. overnight CPAP or NIPPV
    1. improve quality of life
  8. parent self help groups
  9. periodic review @ specialist regional centre
  10. corticosteroids
    1. for ambulant kids w/ DMD
      1. to preserve mobility & prevent scoliosis
    2. prednisolone for 10 days each month
  11. antenatal screening possibly
    1. IDing female carriers
      1. mildly raised CPK
      2. gene deletion detected on DNA analysis
Becker muscular dystrophy
1. some functional dystrophin is made
2. similar features to DMD
  1. but disease progresses more slowly
3. av age of onset= 11 years
4. unable to walk in 20s
5. life expectancy- late 40s to normal
congenital muscular dystrophies
1. heterogenous group
  1. most w/ recessive inheritance
2. present @ birth or early infancy w/
  1. weakness
  2. hypotonia
  3. contractures
3. typically proximal weakness is slowly progressive
  1. w/ tendency to contracture when ability to walk is lost
  2. some may run a more static course
4. biopsy shows dysmorphic features e.g. reduction
  1. in laminin- ECM proteins
  2. in one of glucosyl transferases
5. linked to CNS abnormalities
  1. may -> LD

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Muscle disorders- the muscular dystrophies

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	Created by v.djabatey almost 11 years ago