week 10 --> HD

Question 1

What is huntington disease?

Answer 1

Progressive neurodegenerative disorder with motor, cognitive, pysychiatric disturbance.
Affects mood, movement and memory

Question 2

What are the movement disorders caused by HD?

Answer 2

Chorea, dystonia, bradykinesia, swallowing/ choking, dysarthria

Question 3

What are the mood disorders caused by HD?

Answer 3

Depression, euphoria, apathy, anxiety, aggression, psychotic symptoms

Question 4

What are the cognition disorders caused by HD?

Answer 4

Loss of executive functioning, rigidity of thought, memory loss, dementia

Question 5

What is the median age onset of HD and how survival time after diagnosis?

Answer 5

Mean age of onset is 35 to 44 years but can range from 2-80yrs.

Median survival rate is 15-18 years after onset

Question 6

What does Chorea mean?

Answer 6

Uncrotrolled movemement that you are not expecting to make –> no purpose

Question 7

What is the genetic cause of HD?

Answer 7

Autosomal dominant disorder
Complete penetrance –> everyone that inherit the genetic mutation will get it

HTT gene at 4q16.3

Normal HTT gene contains, within exon 1, a run of CAG trinucleotide repeats

Question 8

What happens to the CAG trinucleotide repeat in a person with HD?

Answer 8

The HD mutation causes expansion of the CAG repeat to be greater than 40. Which is seen as the cut of point for the caue of HD.

Very few cases of 36-39 CAG repeats causing HD.

Question 9

What is the action of HD at protein level?

Answer 9

Abnormal protein – increased number of glutamine amino acids = polyglutamine (polyQ) expansion which alters protein structure and biochemical properties.

PolyQ cellular protein aggregates form – unknown if they cause disease

Question 10

Where in the brain does the abnormal proteins formed by the HD mutation affect?

Answer 10

Basal gnaglia especially caudate nucleus primarily affected

Question 11

What is a definition of anticipation?

Answer 11

The onset of a disorder occurs at an earlier age as it is passed from one generation to the next. Often this is associated with an increase in severity of symptoms

Question 12

What is anticipation assoicated with?

Answer 12

Assoicated wtih triplet repeat disorders

Question 13

What is the consequence of anticpiation on triplet repeat disorders?

Answer 13

Triplet repeat expansions are unstable and may increase (occasionally contract) when passed to the next generation

Question 14

The phenomenon of anticipation is often linked to the gender of the parent. State the high anticipation risk for Hd, Myotonic dystropy and Fragile X syndrome.

Also state the mode of inheritance?

Answer 14

HD–> Autosomal dominant inheritance –> higher anticipiation risk if its from parternal inheritance.

MD –> AD inheritance –> Maternal inheritance

Fragiel X syndrome –> XL recessive –> maternal inheritance

Question 15

What affects the age of onset of HD?

Answer 15

The size of expansion of CAG repeat

Question 16

When is predictive gene testing used for HD?

Answer 16

When the patient is aymptomatic but has a family history of HD. So trying to predict whether or not the person with get HD

Question 17

What is investigated in gene testing for Hd?

Answer 17

The number of CAg repeats

Question 18

What is HD predictive testing?

Answer 18

Different to convential medical testing which defines a person current condition.

It is testing someone who is asymptomatic and predicting in advance whether they will get HD –> cannot tell you when thou and how bad it will be

Question 19

What other diseases can predictive testing be used on?

Answer 19

BRCA (familial breast cancer genes)
HNPCC (Hereditary non-polyposis colon cancer)
Myotonic dystrophy

Question 20

What is the aim of predictive testing in terms of treatment of HD?

Answer 20

Hope that early identification leads to reduced morbidity and mortality through targeted screening, surveillance and prevention

Question 21

What are the treatments of HD?

Answer 21

Symptomatic treatment only at present

No prevention or cure

Testing does not save lives

Question 22

What are reasons for testing for HD?

Answer 22

Just ‘want to know’
Plan future care
Want to plan their career
Make decisions about children
Inform other relatives whose risk may change

Question 23

What is the chance of a child having HD if one of there parents have it?

Answer 23

50%

Question 24

Can a embryo be tested for HD?

Answer 24

Yes a genetic test of the embryo can be done and the ones with the HD mutation can be discarded

Question 25

What is the limitations of predictive testing?

Answer 25

While if positive is certanity of full penetrance it does not tell you how bad it will be, when will it happen and the course.

Question 26

What do you need to consider in Hd predictive testing?

Answer 26

Insurance
Changing risk to others  children can all of a sudden become more at risk

Impact on current relationships – and future..

Psychological impact

No medical advances yet