muscular dystrophies Flashcards

1
Q

by what mechanisms can muscular dystrophies occur?

A

loss of structural proteins

defective enzymes

disruption of sarcolemma-repair mechanisms

loss of signaling molecules

non coding region mutations

defective post translational modifications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are muscular dystrophies?

A

inherited diseases

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

muscular dystrophes can be classified either by

A

historical classification ie duchenne muscular dystrophe

clinical phenotype

inheritance ( Gene) / x linked

underlying genetic cause eg DMD-dystrophinopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is duchenne muscular dsystrophy?

A

x linked muscular dystrophe Xp21

dystrophic localised at the sarcolemma- dystrophinopathy

depending on mutation may get a milder becker phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

when does the Becker phenotype of DMD occur?

A

when dystrophin is produced in frame deletions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what causes DMD

A

large deletions, duplications and point mutations that disrupt the reading frame and tend to cause the absense of dystrophin and DMD phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how does Duchenne Muscular Dystrophe present ?

A

usually with delayed milestones

wheelchair by 13 years old

cardiac involvement (100% after 18)

respiratory involvement
survival beyond 30 is unusual

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how does becker muscular dystrophe present?

A

later onset than DMD and ambulant in to 20s

worse cardiac involvement

mean age of death mid 40s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is DMD- associated DCM?

A

mutations in the promoter or exon 1
No dystrophin in cardiac muscle
little or no skeletal muscle involvement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what treatment is available for DMD?

A

Supportive
Scoliosis corrective surgery as children
Manage congestive cardiac failure and arrythmias
beta blocker, ACE inhibitor, transplantation
NIV for respiratory failure
Steroids
Gene therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how do steroids work in DMD?

A

mechanisms unclear as other immunosuppressants do not have similar effect

slows down disease progression

start when motor functions plateau stop when non-ambulant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

how can gene therapy improve outcome for DMD

A

anti sense oligonucleotides - weekly s/c injectons

  • PTC 124 (Ataluren) oral drug that promotes ribosomal read-through of nonsense (stop) mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is myotonic dystrophy

A

commonest type of muscular dystrophy

onset in adulthood
congenital
late onset
oligosymptomatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how does adult onset Myotonic dystrophe present

A
muscle weakness
myotonia
cataracts
cardiac conduction defects
cognitive changes
GI disturbances
diabetes
male hypogonadism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how can myotonic dystrophe be treaed

A

supportive

cardiac complications

experimental AON knockdown of expansions?

fleicanide or mexilitine for symptom relief of myotonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is FSH dystrophy?

A

facialscapulohumeral muscular dystrophy

typically presents before 20 years of age

scapular fixators and ankle dorsiflexor weakness

can lead to retinal telangectasia and sensorineural hearing loss

20% need wheelchair

normal life expectancy