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Flashcards in Genetics of CNS Disease Deck (31):
1

what type of inheritance is duchennes muscular dystrophy?

x linked recessive in gene which codes for dystrophin

2

what is the progression of DMD?

onset of weakness = 3-4 yrs (pelvic and shoulder girdles)

wheelchair bound by 10-12 years

death from resp and cardiac muscles in 20s

3

what is the tell tale signs of DMD?

classic posture

calf hypertrophy

gower's sign

toe walking

4

what type of mutation is DMD?

large scale deletions in 70%

point mutations, small insertions and deletion in remaining 30%

5

what investigations take place in DMD?

raised CK
EMG
muscle biopsy
molecular genetic testing

6

what is a differential diagnosis of DMD?

autosomal recessive limb girdle muscular dystrophies (some caused by sarcoglycan deficiencies)

7

what is huntington disease?

progressive neurodegenerative disorder

8

what age does HD usually occur?

between 30 and 50

9

what is progression of HD?

involuntary movements
dementia
progression to severe dependency and death

10

what pattern of inheritance is HD and what does penetrance depend on?

autosomal dominant

depends on age

11

what are early clinical signs of HD?

clumsiness
agitation / irritability
apathy
anxiety / depression
delusions
disinhibition
abnormal eye movements

12

what are the later clinical signs of HD?

dystonia
trouble with balance and dexterity
slow voluntary movement
weight loss
speech difficulties
bradykinesia
chorea
inability to walk and speak
swallowing problems
inability to care for self

13

what does HD classically look like pathologically / on imaging?

caudate atrophy

14

what is the specific molecular genetic defect in HD?

normal = CAG which codes for glutamine repeated 20 times

HD = repeated 42 times

15

how is HD diagnosed?

predictive testing using PCR

16

does any treatment exist for HD?

no, just coping strategies

17

what is spinal muscular atrophy?

progressive loss of anterior horn cells in spinal cord and brain stem nuclei

18

what are symptoms of spinal muscular atrophy?

hypotonia
proximal muscle weakness
tongue fasciculation

19

what age does SMA come on?

variable age and rate of progression (types 0, I, II, III and IV)

20

what pattern of inheritance is SMA?

autosomal recessive

21

what gene is affected in SMA?

SNM1

22

who does SMA more commonly affect?

children (types 0 and I)

23

how can SMA be treated?

by altering splicing of SMN2 mRNA by a synthetic oligonucleotide (Nusinersin)

24

what is the most common cause of dementia?

alzheimers

25

is family clustering seen in pre-senile alzheimers or old age?

both

26

what is the pathology of alzheimers disease?

loss of cortical neurones

neurofibrillary tangles (intracellular)

senile plaques (extracellular)

27

what are senile plaques?

extracellular protein deposits containing amyloid B protein

28

what can be genetic cause of alzheimers?

autosomal dominant trait in 5-10% cases (early onset)

downs syndrome (onset in 3rd or 4th decade)

29

what genes could be affected in autosomal dominant alzheimers?

APP mutations (chromosome 21)

presenilin 1 (chromosome 14)

presenilin 2 (chromosome 1)

30

how does ApoE contribute to alzheimers?

e4 predisposes to alzheimers

e4/e4 = 55% affected by 80
e3/e4 = 27% affected by 85
no e4 = 9% affected by 85

31

what causes multiple sclerosis?

multifactorial with some clustering in families