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Flashcards in Huntington's disease Deck (29)
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1
Q

What is HD?

A

Autosomal dominant neurodegenerative condition

2
Q

Pathogenesis of HD

A

CAG trinucleotice repeat disease only chromosome 4
Faulty Huntingtin protein produced - expanded glutamine in the protein making it toxic
Affects caudate nucleus in striatum
Loss of cholinergic interneurones

3
Q

What is huntingtin involved in?

A

Gene expression
Intracellular transport and signalling
Mitochondrial function
Apoptosis

4
Q

CAG healthy repeats

A

10-26

27-35 = not got HD but risk of expansion causing HD in offspring

5
Q

Pathological CAG repeats

A

36+

More repeats causes more severe disease and quicker progression

6
Q

What are the main areas of HD symptoms?

A

Cognitive decline
Affective -mood
Motor - chorea

7
Q

Treatments for HD

A

No cure or disease modifying treatments
Only symptomatic treatment
Requires MDT

8
Q

HD MDT

A
Patient
Carter
Regional care advisor
GP
Psychologist
Psychiatrist
Speech and language therapists
Dietician
Social services
Geneticist
Neurologist
9
Q

Treatments to reduce chorea

A
ATypical and typical antipsychotics
Tetrabenazine 
Anxiety treatment 
Myoclonus treatment = anticonvulsant
Bruxism treatment = botox
10
Q

What do antipsychotics do?

A

Deplete dopamine

11
Q

Tetrabenazine

A

Dopamine depleting agent

Problems with mood impairment

12
Q

Anxiety treatment in HD

A

Clonazepam

13
Q

What is bruxism?

A

Grinding of teeth
Gnashing
Clenching of teeth

14
Q

what is penetrance?

A

proportion of people with a particular genetic change who exhibit signs and symptoms of a genetic disorder

15
Q

typical age of onset

A

35-50

can be juvenile onset = <20

16
Q

life expectancy of someone with HD

A

most people die 20-30 years after a diagnosis/ start of symptoms

17
Q

36-39 CAG repeats

A

show incomplete penetrance

many are asymptomatic into old age

18
Q

over 40 CAG repeats

A

complete penetrance

more repeats = earlier onset of disease

19
Q

anticipation

A

instability of CAG repeats

expansion occurs greatest during spermatogenesis

20
Q

juvenile disease

A

> 60 CAG repeats

21
Q

27-35 CAG repeats

A

no risk to individual but could expand and cause huntington’s in offspring

22
Q

when is prenatal genetic testing done?

A

only when the couple plan to terminate an affected fetus as there is no point in risking the fetus if it will be carried to term irrelevant of the result. Also if the fetus was affected they would have received a diagnosis without consent

23
Q

how to prevent inheritance of huntington’s

A

prenatal testing

IVF and embryo screening

24
Q

testing offspring without testing parents

A

this can be done by looking for markers associated with huntington’s rather than looking for CAG repeats first

25
Q

genetic testing in twins

A

need to come to a joint decision

requires careful counselling

26
Q

pathogenesis of huntington’s disease

A

loss of cholinergic interneurons of striatum which are part of the indirect pathway
imbalance between indirect and direct pathway causing favour of direct pathway
excessive activation of motor pathways

27
Q

treatment for hyperkinetic activity in huntington’s

A

tetrabenazine

28
Q

how does tetrabenazine work?

A

inhibits dopamine uptake into synaptic vesicles of presynaptic neurons
less dopamine released from substantia nigra so there is less inhibition of the indirect pathway and activation of it

29
Q

effect on ventricles

A

reduced size