Neurogenetics Flashcards

1
Q

Duchenne inheritance

A

X-linked recessive

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2
Q

What age does onset of weakness occur in duchenne’s?

A

3-4 years

  • pelvic and shoulder girdles
  • wheelchair bound by 10-12 years
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3
Q

Why do people with duchenne’s die?

A

Involvement of cardiac and respiratory muscles (weakness etc)

-usually die in their 20’s

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4
Q

Which conditions might you see calf hypertrophy in?

A

DMD and Becker’s

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5
Q

What modification of the dystrophin gene leads to duchenne’s?

A
  • Large scale deletions of dystrophin gene in 70% of DMD boys
  • Point mutations, small insertions and deletion in remaining 30%
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6
Q

What else might cause a muscular dystrophy?

A

Sarcoglycan deficiencies

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7
Q

Huntington inheritance

A

Autosomal dominant

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8
Q

Features of Huntington’s disease

A
  • Involuntary movements
  • Depression
  • Progression to severe dependency and death over 15-20 years
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9
Q

Early clinical signs of huntington’s

A
Clumsiness
Irritability 
Agitation
Apathy 
Anxiety 
Abnormal eye movements
Disinhibition 
Delusions Hallucinations  
Depression
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10
Q

Gowers sign

A

DMD

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11
Q

Toe-walking

A

DMD

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12
Q

How would you diagnose DMD?

A
  • raised serum CK
  • EMG
  • muscle biopsy
  • molecular genetic testing (screen for deletions)
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13
Q

DDX for DMD?

A

Autosomal recessive limb girdle muscular dystrophies - caused by sarcoglycan deficiencies

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14
Q

Onset of Huntington’s

A

Onset between ages 30 and 50

age dependent penetrance - variable

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15
Q

Caudate atrophy in which disease?

A

Huntington’s

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16
Q

CAG repeats and Huntington’s

A

Disease becomes penetrant when you get 40+ CAG repeats

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17
Q

Age dependent penetrance and Huntington’s

A

age 20: 1 in 2
age 50: 1 in 3
age 70: 1 in 11

(i.e. if no symptoms the older you get, the less likely you are to develop HD)

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18
Q

Predictive testing available for HD

A
  • pre-natal testing

- pre-gestational testing

19
Q

Loss of cortical neurones
Neurofibrillary tangles
Senile plaques

A

Alzheimer’s disease

20
Q

The name given to extra-cellular protein deposits containing amyloid beta protein?

A

Senile plaques

21
Q

Inheritance of hereditary dementia? (early onset)

A

Autosomal dominant

22
Q

When might people with Down syndrome develop dementia?

A

3rd or 4th decade

23
Q

What does e4 allele predispose? (this allele is on the ApoE gene)

A

e4 predisposes to Alzheimer disease

-e2 is associated with longetivity

24
Q

MS risk for 1st degree relatives

A

3%

25
Q

MS risk for 2nd degree relatives

A

1%

26
Q

Population risk of MS

A

0.2%

27
Q

Twin studies in MS

A

Monozygotic twins - 25%

Dizygotic twins - 3%

28
Q

DMD incidence

A

1/3000

29
Q

DMD signs of muscle weakness

A

Gower’s sign

Toe walking

30
Q

What carrier testing can you offer in DMD?

A
  • you can identify the mutation in boys
  • using this, you can then ask the females in the family if they want to find out whether they are carriers or not
  • female carriers can then be offered pre-natal testing
31
Q

Huntington disease incidence

A

1/20 000

32
Q

Early clinical signs

A
Clumsiness
Agitation
Irritability 
Apathy 
Anxiety 
Disinhibition 
Delusions Hallucinations 
Abnormal eye movements 
Depression
33
Q

Later clinical signs

A
Dystonia 
Involuntary movements 
Trouble with balance and walking 
Trouble with activities that require manual dexterity 
Slow voluntary movements
Difficulty initiating movement 
Inability to control speed and force of movement 
Weight loss 
Speech difficulties 
Stubbornness
34
Q

Very late clinical signs

A
Rigidity 
Bradykinesia (difficulty initiating and continuing movements) 
Severe chorea (less common) 
Serious weight loss 
Inability to walk 
Inability to speak 
Swallowing problems, danger of choking 
Inability to care for oneself
35
Q

What does CAG code for?

A

Glutamine

36
Q

Atrophy in which part of the brain especially, in HD?

A

Caudate nucleus

37
Q

What testing can you give for huntington’s disease?

A

Predictive testing: prenatal and pre-gestational

38
Q

Amyloid beta protein is a fragment of what?

A

Fragment of the product of the APP gene 21

APP –> amyloid precursor protein

39
Q

Chromosome mutations associated with AD alzheimer’s disease?

A
APP mutations (chromo 21)
Presenilin 1 (chromo 14)
Presenilin 2 (chromo 1)
40
Q

e3

A

Most common

41
Q

e2

A

Associated with longetivity

42
Q

e4

A

Associated with AD alzheimers

43
Q

Difference between e3/e4 and e4/e4

A

e3/e4 –> 27% affected by 80 years

e4/e4 –> 55% afected by 85 years