Huntington's Disease (16)

Question 1

Huntington’s Disease (HD)

Answer 1

A progressive neurodegenerative disorder with motor, cognitive and psychiatric disturbances

Question 2

Movement symptoms of HD

Answer 2

Chorea (uncontrolled), dystonia (long muscle contraction), bradykinesia - swallowing/choking, dysarthria

Question 3

Mood symptoms of HD

Answer 3

Depression, euphoria, apathy (can’t find energy to do things but happy), anxiety, aggression, psychotic symptoms

Question 4

Cognitive symptoms of HD

Answer 4

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

Question 5

Mean age of onset of HD

Answer 5

35-44 years

Question 6

Range of age of onset of HD

Answer 6

2-80 years

Question 7

Median survival after onset

Answer 7

15-18 years

Question 8

What type of inheritance is HD?

Answer 8

Autosomal dominant

Question 9

How penetrant is HD?

Answer 9

Complete penetrance

Question 10

What gene is effect in HD?

Answer 10

HTT gene at 4q16.3

Question 11

The normal HTT gene within an exon contains

Answer 11

A run of CAG trinucleotide repeats

Question 12

The HD mutation

Answer 12

An expansion of CAG repeats >40 (some 36-39)

Question 13

Everyone has how many copies of HTT gene?

Answer 13

2

Question 14

What is the problem with polyglutamine expansion?

Answer 14

Alters protein structure and biochemical properties, aggregate together (unknown if cause or not)

Question 15

What is primarily affected by HD mutation?

Answer 15

Basal ganglia, especially caudate nucleus

Question 16

Anticipation

Answer 16

The onset of a disorder occurs at an early age and is passed from one generation to the next, often with an increase in severity of symptoms

Question 17

Anticipation and triple repeat disorders

Answer 17

TR expansions are unstable and may increase when passed to next generation

Question 18

Anticipation and gender

Answer 18

• HD increase risk of anticipation if parental inheritance

- Myotonic dystrophy (AD) and Fragile X syndrome (XL recessive) if maternal inheritance

Question 19

Predictive testing

Answer 19

The use of genetic test in an asymptomatic person to predict future risk of disease

Question 20

Disease where predictive testing is possible

Answer 20

BRCA, HNPCC (Hereditary Non-Polyposis Colon Cancer) and Myotonic dystrophy

Question 21

Advantages for testing

Answer 21

• Just ‘want to know’
• Plan future care
• Want to plan career
• Make decisions about children
• Inform relative who may be at risk
• Need certainty

Question 22

Disadvantages for testing

Answer 22

• Insurance
• Changing risk to others
• Impact on relationships
• Psychological impact
• No medical advances yet

Question 23

How many people drop out of HD predictive testing?

Answer 23

50-60% (some come back)