20.03.04 AR disorders - i.e. SMA Flashcards
1
Q
Estimated incidence of SMA
A
1 in 6- 10,000
2
Q
Carrier frequency of SMA
A
1 in 50 in UK
3
Q
Is it a common cause of infant death
A
Yes, second most common AR disorder after CF.
4
Q
What is the pathology of SMA
A
- spinal cord and anterior horn motor neuron degeneration.
- The result of synaptic defects in motor neuromuscular junctions (NMJs)
5
Q
Clinical phenotype
A
- Progressive proximal limb and trunk muscle weakness
- Breathing difficulties (intercostal muscle weakness)
- paralysis of voluntary muscles
- Tremor in fingers
- Tongue fasiculations, poor suck and swallow.
6
Q
What is prenatal SMA
A
- Severe weakness of prenatal onset
- Arthrogryposis multiplex congenita. Congenital joint contractures, absence of movement (except face and extraocular), death from respiratory arrest before 1 month of age.
7
Q
What is type I SMA
A
- 60% of all SMA.
- Diagnosed before 6 months age.
- Floppy baby= profound hypotonia, tongue fasiculations, lack of motor development
- Progressive weakness in infancy and death at an early age (often due to aspiration pneumonia)
8
Q
What is type II SMA
A
- Intermediate subtype. 27% of SMA cases
- Onset between 6-12 months
- Low muscle tone, absent tendon reflexes. Can sit unaided but never able to walk
- Reduced life expectancy (70% reach adulthood)
9
Q
What is type III SMA
A
- 12% of SMA patients
- Onset of muscle weakness ~ after 10 months (IIIa) or 3 years (IIIb)
- Can stand and are ambulatory (probability decreases with age)
10
Q
What is type IV SMA
A
- 1% of SMA patients
- Onset of muscle weakness in 2nd or 3rd decade of life
- Can stand and walk alone
11
Q
What is atypical SMA
A
- SMA with congenital bone fractures.
- Floppiness, multiple fractures of long bones, CNS involvement and elevated CK levels
12
Q
Differential diagnosis for floppy babies
A
- SMA
- DM1
- PWS
13
Q
Which genes are associated with SMA
A
- SMN1 and 2
- 5q12.2-13.3
14
Q
SMA is caused by what
A
-Hom or het deletions/ mutations in SMN1
15
Q
How are SMN1 and 2 arranged
A
- SMN1 is telomeric
- SMN2 is centromeric