lecture 33 Flashcards
What causes DMD?
- loss of dystrophin
What is the mouse model for DMD?
mdx
What are dystrophinopathies?
- DMD
- BMD
- familial cramps and myalgia syndrome
- other
→ x-linked dilated cariomyopathy
→ isolated elevated CK
→ manifesting carrier females
→ isolated quadriceps myopathy
What is the onset/incidence/diagnosis of DMD/BMD?
DMD: onset 5 years
- incidence 1/35,000 male birhts
- clinical onset variable
→ wheelchair dependency > 16 years
What are the clinical presentations of DMD?
- delayed motor milestones
→ mean age walking 18m (normal s manoeuvre
→ persistent toe-walking, (less commonly) flat feet - fatigability, frequent falls
→ inability to run or to keep up with peers - calf/thigh cramps, muscle hypertrophy
- speech delay, learning problems
What do you see in physical examination of a patient with DMD?
- waddling gait
- proximal weakness
- enlarged, rubbery muscles
→ calves +/– quads, gluteal, deltoid, even tonuge
→ early hypertrophy, late pseudohypertrophy - facial muscles spared
- extra-ocular muscles always spared
- weak neck flexors
- lumbar lordosis
- usually never had the ability to jump
What is muscle hypertrophy?
- muscles look larger but infact this apparent enlargement is due to increased fat and fibrosis rather than an increase in true muscle tissue i.e. ‘pseudohypertrophy’
What is gowers’ sign?
- has to roll over
- pushes up
- walks up knees with hands
- important neurologic sign
- climbing up legs on arising from ground
- indicative of proximal weakness in older children (>4 years)
- normal in younger children <3 years
- non-specific i.e. seen in any muscle disorder causing proximal weakness
→ DMD, BMD
→ myotonic dystrophy
→ congenital myopathies
→ muscle disorders of adulthood including steroid myopathy
What is muscle atrophy?
- thinned muscles
How is DMD diagnosed?
- serum creatine kinase level
→ enzyme released by damaged muscle cells intp blood
→ normal 10,000 - thyroid functiont ests (blood)
→ hypothyroidism can look very much like DMD - genetic testing by MLPA for DMD
→ positive in 65-70% of cases
→ deletions 65%, duplications 5%, point mutations 10-15% - muscle biopsy
→ high suspicion of DMD, genetic tests are negative
→ necessary in about 1/3 of cases
What is seen regarding serum CK levels?
normal (100 U/L)
- congenital muscular dystrophies
- FSH MD
- Duchenned and Becker MD
- limb girdle MD
very broad differential diagnosis
What is the natural history of DMD?
3 - 6 years: ‘honeymoon’ phase
- mild weakness but overall strength and function may increase
- increasing disparity between affected child and his peers
8 years: difficulty climbing stairs, walking
- increasing fatigability, inability to run and jump
- increasingly prominent lumbar lordosis
- progressive contractures Achilles, ITBs, hips
~10-13 years: transition to wheelchair use
respiratory or cardiac failure late teens - early 20s
What is the course of DMD?
- some variability in course
- ambulation lost anywhere between 8-14 years
- gradual decline in upper limb function: difficult bringing hands to mout by 16-18 years
- death average approx 25 years
- death is usually from respiratory failure
- cardiac death in about 10%: cardiomyopathy or arrhythmias
What is the natural history of Becker MD?
- onset after age 5 years
→ commonly 5 - 15 years
→ occasionally as late as 3rd or 4th decade - progressive limb-girdle weakness
- calf pain and myalgias common
- able to walk after 15 years
- respiratory failure after 4th decade
- cardiomyopathy is MORE common than in DMD
→ greater strain caused by greater exercise and activity
What is the respiratory deficit in DMD?
- weakness of intercostal muscles > diaphragm
- in the early years, vital capacity increases with age and growth
- in the early teens, vital capacity plateaus ajnd then declines steadily (5-10%/year)
- resipiratory failure typically occurs in the late teens or early 20s
