Huntingtons Disease - OB

Question 1

What disease did George Huntington originally report a genetic component, tendenct to insanity or suicide that manifest as a grave disease in adult life ?

Answer 1

Chorea

Question 2

HD Genetics

Answer 2

Passed down by females and males
Mitochondrial disease inherited only from mum
Monogenic- one gene causes the disease

Question 3

What is the difference between monogenic, polygenic and heterogenic ?

Answer 3

Monogenic- one gene causes the disease
Heterogenic – caused by different genes
Polygenic – interaction of many different genes

Question 4

What is shown within families with the Htt mutation ??

Answer 4

– large family variation in clinical manifestations of exactly the same gene

Question 5

IT15

Answer 5

Trinucleotide repeat disorder
Number of CAG= Glutamine is increased
Normally up to 35 triplets
Pathological – 40 or more definitely develop Huntington disease

Question 6

Genetic testing

Answer 6

Predictive testing possible
- Pre natal testing- abortions very sensitive issues
- Pre implantation diagnosis – 8 cell stage of fusion – can test cells then decide if you put them back in the womb
- More healthy babies being born as a result of testing
50/50 likelihood in offspring of HD patients

Question 7

Exact role of huntingtin isn’t fully known

Answer 7

Most people have a repeat length of 16-20
Correlation between age of onset vs number of triplets
Variation of age and repeat length not a case of set age for set number of repeats

Question 8

What repeat length is most common in Huntington

Answer 8

16-20

Question 9

What part of the Basal ganglia is mainly affected in huntingtons ?

Answer 9

Striatum of the Basal Ganglia

Question 10

What causes cortical atrophy ?

Answer 10

High expression of huntingtin

- NB. More repeats the more pathogneic the protein likely to be

Question 11

HD Movement

Answer 11

• Chorea – random dance like often generalised
• Tics – rapid and stereotypical/ focused
• Dystonia – slow, localosed and associated with abnormal posture
• Myoclonus – very fast, stereotypical/ fous or random/generalised
• Habit

Question 12

Chorea

Answer 12

– random dance like often generalised

Question 13

Tics

Answer 13

rapid and stereotypical/ focused

Question 14

Dystonia

Answer 14

slow, localised and associated with abnormal posture

Question 15

Myoclonus

Answer 15

very fast, stereotypical/ focus or random/generalised

Question 16

Management of chorea

Answer 16

• Blockage of DA receptors
• Due to excess of dopamine in Basal ganglia
• Induce pre synaptioc release of dopamine
• Or blocking post synaptic DA receptors

Question 17

Effect of tetrabenazine on chorea

Answer 17

• Small improvement
• 26 chose not to continue – essentially half
• Parkinsonism increased
• Depression and anxiety side effects

Question 18

Chorea in HD

Answer 18

follows the inverted U shape eventually dies down by itself anti chorea medication not necessary in severe stages

• Gait cant really be treated neither can they treat cognitive impairment
• Instead > coping mechanisms
• Concentrate on one thing at a time

Question 19

Psychiatiric manifestations

Answer 19

• depression and anxiety > treated aggresively in HD
• increased irritability
• violence
• Apathy
• Psychosis- antipsychotic

Question 20

Disease modifying therapy

Answer 20

different approaches

Downreg of mutant huntingtin protein

Question 21

Clinical

Answer 21

Multidisciplinary treatment