Huntington's disease Flashcards
What is HD?
Autosomal dominant neurodegenerative condition
Pathogenesis of HD
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
What is huntingtin involved in?
Gene expression
Intracellular transport and signalling
Mitochondrial function
Apoptosis
CAG healthy repeats
10-26
27-35 = not got HD but risk of expansion causing HD in offspring
Pathological CAG repeats
36+
More repeats causes more severe disease and quicker progression
What are the main areas of HD symptoms?
Cognitive decline
Affective -mood
Motor - chorea
Treatments for HD
No cure or disease modifying treatments
Only symptomatic treatment
Requires MDT
HD MDT
Patient Carter Regional care advisor GP Psychologist Psychiatrist Speech and language therapists Dietician Social services Geneticist Neurologist
Treatments to reduce chorea
ATypical and typical antipsychotics Tetrabenazine Anxiety treatment Myoclonus treatment = anticonvulsant Bruxism treatment = botox
What do antipsychotics do?
Deplete dopamine
Tetrabenazine
Dopamine depleting agent
Problems with mood impairment
Anxiety treatment in HD
Clonazepam
What is bruxism?
Grinding of teeth
Gnashing
Clenching of teeth
what is penetrance?
proportion of people with a particular genetic change who exhibit signs and symptoms of a genetic disorder
typical age of onset
35-50
can be juvenile onset = <20
life expectancy of someone with HD
most people die 20-30 years after a diagnosis/ start of symptoms
36-39 CAG repeats
show incomplete penetrance
many are asymptomatic into old age
over 40 CAG repeats
complete penetrance
more repeats = earlier onset of disease
anticipation
instability of CAG repeats
expansion occurs greatest during spermatogenesis
juvenile disease
> 60 CAG repeats
27-35 CAG repeats
no risk to individual but could expand and cause huntington’s in offspring
when is prenatal genetic testing done?
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
how to prevent inheritance of huntington’s
prenatal testing
IVF and embryo screening
testing offspring without testing parents
this can be done by looking for markers associated with huntington’s rather than looking for CAG repeats first
genetic testing in twins
need to come to a joint decision
requires careful counselling
pathogenesis of huntington’s disease
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
treatment for hyperkinetic activity in huntington’s
tetrabenazine
how does tetrabenazine work?
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
effect on ventricles
reduced size
