Huntington's disease

Question 1

What is HD?

Answer 1

Autosomal dominant neurodegenerative condition

Question 2

Pathogenesis of HD

Answer 2

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

Question 3

What is huntingtin involved in?

Answer 3

Gene expression
Intracellular transport and signalling
Mitochondrial function
Apoptosis

Question 4

CAG healthy repeats

Answer 4

10-26

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

Question 5

Pathological CAG repeats

Answer 5

36+

More repeats causes more severe disease and quicker progression

Question 6

What are the main areas of HD symptoms?

Answer 6

Cognitive decline
Affective -mood
Motor - chorea

Question 7

Treatments for HD

Answer 7

No cure or disease modifying treatments
Only symptomatic treatment
Requires MDT

Question 8

HD MDT

Answer 8

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

Question 9

Treatments to reduce chorea

Answer 9

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

Question 10

What do antipsychotics do?

Answer 10

Deplete dopamine

Question 11

Tetrabenazine

Answer 11

Dopamine depleting agent

Problems with mood impairment

Question 12

Anxiety treatment in HD

Answer 12

Clonazepam

Question 13

What is bruxism?

Answer 13

Grinding of teeth
Gnashing
Clenching of teeth

Question 14

what is penetrance?

Answer 14

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

Question 15

typical age of onset

Answer 15

35-50

can be juvenile onset = <20

Question 16

life expectancy of someone with HD

Answer 16

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

Question 17

36-39 CAG repeats

Answer 17

show incomplete penetrance

many are asymptomatic into old age

Question 18

over 40 CAG repeats

Answer 18

complete penetrance

more repeats = earlier onset of disease

Question 19

anticipation

Answer 19

instability of CAG repeats

expansion occurs greatest during spermatogenesis

Question 20

juvenile disease

Answer 20

> 60 CAG repeats

Question 21

27-35 CAG repeats

Answer 21

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

Question 22

when is prenatal genetic testing done?

Answer 22

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

Question 23

how to prevent inheritance of huntington’s

Answer 23

prenatal testing

IVF and embryo screening

Question 24

testing offspring without testing parents

Answer 24

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

Question 25

genetic testing in twins

Answer 25

need to come to a joint decision

requires careful counselling

Question 26

pathogenesis of huntington’s disease

Answer 26

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

Question 27

treatment for hyperkinetic activity in huntington’s

Answer 27

tetrabenazine

Question 28

how does tetrabenazine work?

Answer 28

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

Question 29

effect on ventricles

Answer 29

reduced size