Flashcards in muscular dystrophies Deck (16):
by what mechanisms can muscular dystrophies occur?
loss of structural proteins
disruption of sarcolemma-repair mechanisms
loss of signaling molecules
non coding region mutations
defective post translational modifications
what are muscular dystrophies?
causing progressive weakness and wasting of muscles
replacement of muscle tissue with fibrous connective tissue
cardiac involvement, respiratory involvement seen in some
CNS tissue not usually affected
muscular dystrophes can be classified either by
historical classification ie duchenne muscular dystrophe
inheritance ( Gene) / x linked
underlying genetic cause eg DMD-dystrophinopathy
what is duchenne muscular dsystrophy?
x linked muscular dystrophe Xp21
dystrophic localised at the sarcolemma- dystrophinopathy
depending on mutation may get a milder becker phenotype
when does the Becker phenotype of DMD occur?
when dystrophin is produced in frame deletions
what causes DMD
large deletions, duplications and point mutations that disrupt the reading frame and tend to cause the absense of dystrophin and DMD phenotype
how does Duchenne Muscular Dystrophe present ?
usually with delayed milestones
wheelchair by 13 years old
cardiac involvement (100% after 18)
survival beyond 30 is unusual
how does becker muscular dystrophe present?
later onset than DMD and ambulant in to 20s
worse cardiac involvement
mean age of death mid 40s
what is DMD- associated DCM?
mutations in the promoter or exon 1
No dystrophin in cardiac muscle
little or no skeletal muscle involvement
what treatment is available for DMD?
Scoliosis corrective surgery as children
Manage congestive cardiac failure and arrythmias
beta blocker, ACE inhibitor, transplantation
NIV for respiratory failure
how do steroids work in DMD?
mechanisms unclear as other immunosuppressants do not have similar effect
slows down disease progression
start when motor functions plateau stop when non-ambulant
how can gene therapy improve outcome for DMD
anti sense oligonucleotides - weekly s/c injectons
- PTC 124 (Ataluren) oral drug that promotes ribosomal read-through of nonsense (stop) mutations
what is myotonic dystrophy
commonest type of muscular dystrophy
onset in adulthood
how does adult onset Myotonic dystrophe present
cardiac conduction defects
how can myotonic dystrophe be treaed
experimental AON knockdown of expansions?
fleicanide or mexilitine for symptom relief of myotonia