Huntington's

Question 1

what inheritance does Huntington’s show

Answer 1

autosomal dominant

Question 2

does Huntington’s affect men or women more

Answer 2

equally

Question 3

what is the relation between number of CAG repeats and disease

Answer 3

the more repeats, the earlier the age of onset and the more severe disease?

Question 4

average age of onset of Huntington’s

Answer 4

middle age

Question 5

genetic basis for Huntington’s

Answer 5

• there is expansion of the CAG trinucleotide repeat on the gene that encodes for teh huntingtin protein
• this leads to an elongated polyglutamine tail on the huntingtin protein (as each CAG codes for glutamine)
• this is a toxic ‘gain of function’ mutation and is damaging to cells - causes neurodegeneration

Question 6

which chromosome is the huntingon gene found on

Answer 6

4

Question 7

anticipation

Answer 7

with each generation, there are more trinucleotide repeats - earlier onset of disease

Question 8

does anticipation occur in males and females

Answer 8

more common when passed down from males, as the CAG trinucleotide repeat is particualrly unstable during spermatogenesis in meiosis

Question 9

how many repeats mean risk of expression of disease, and definite expression

Answer 9

normal is about <26

>35 - increased risk, reduced penetrance

≥40 - will develop it disease they live a normal life span

Question 10

what is the penetrance like

Answer 10

complete penetrance - all gene carriers will develop the disease eventually

Question 11

which area of teh brain is primarily affected

Answer 11

the striatum

Question 12

pathology of Huntington’s

Answer 12

primarily there is atrophy and neuronal loss of the striatum (caudate nucleus and putamen)

there is 2y atrophy to the global pallidus

later, there is compensatory ventricle expansion and ifnally cortical atrophy in frontal and parietal areas

Question 13

what happens to GABA

Answer 13

there is degeneration of the neurons that secrete GABA, loss of GABA inhibition results in hyperactivity of the thalamocortical feedback pathyway - chorea

Question 14

what happens to dopamine levels?

Answer 14

thye are unchanged, so pt can initiate movements, unlike in PD

however due to loss of GABA may find it hard to stop movement –> chorea

Question 15

clinical features

Answer 15

• cognitive impairement
• behavioural features
• motor features

Question 16

what is chorea

Answer 16

• random movements of fingers/toes, occasional peculiar postures of body parts and odd facial expressions are typical of early disease
• like can intiate movement byt not stop it

Question 17

can pt suppress chorea

Answer 17

sometimes for short periods of time - observe for several minutes

Question 18

dementia and Huntington’s

Answer 18

occurs early in disease course, onset is subtle

there is impaired judgement and slowed thinking, loss of executive function

Question 19

what investigations looking at genes can be done

Answer 19

CAG repeat testing

Question 20

imaging

Answer 20

MRI or CT will show cortical and striatal atrophy, enlarged ventricles

Question 21

how long do peoplem with Huntington’s live from disease onset

Answer 21

around 15 years

Question 22

what are 2 common causes of death

Answer 22

aspiration pneumonia due to discoordinated swallowing

suicide