(16+17) Huntington's Disease

Question 1

What is Huntington Disease (HD)?

Answer 1

Progressive neurodegenerative disorder with motor, cognitive and psychiatric disturbances. Affects movements, memory and mood

Question 2

In what ways does HD affects movement?

Answer 2

• chorea
• dystonia
• bradykinesia
• swallowing/choking
• dysarthria

Question 3

What is chorea?

Answer 3

A neurological disorder characterized by jerky involuntary movements affecting especially the shoulders, hips, and fac

Question 4

What is dystonia?

Answer 4

A state of abnormal muscle tone resulting in muscular spasm and abnormal posture

Question 5

What is bradykinesia?

Answer 5

Bradykinesia means slowness of movement. Weakness, tremor and rigidity may contribute to but do not fully explain bradykinesia

Question 6

What is dysarthria?

Answer 6

Difficult or unclear articulation of speech that is otherwise linguistically normal

Question 7

In what way does HD affect mood?

Answer 7

• depression
• euphoria
• apathy
• anxiety
• aggression
• psychotic symptoms

Question 8

In what way does HD affect cognition?

Answer 8

• loss of executive functioning
• rigidity of thought
• memory loss
• dementia

Question 9

What is the mean age of onset of HD?

Answer 9

35 to 44 years (range 2-80 years)

Question 10

What is the median survival time of HD?

Answer 10

15 to 18 years after onset

Question 11

What type of genetic disorder is HD?

Answer 11

Autosomal dominant

Question 12

Does HD have complete or incomplete penetrance?

Answer 12

Complete

Question 13

Where is the HTT gene?

Answer 13

4q16.3

Question 14

What does a normal HTT gene contain?

Answer 14

A run of CAG trinucleotide repeats within exon 1

Question 15

What does the HD mutation in the HTT gene consist of?

Answer 15

An expansion of the CAG repeats (>40 repeats)

a few people develop HD with CAG repeats of 36-39

Question 16

What is the normal Huntingtin protein?

Answer 16

3144 amino acids

Widely expressed in different tissues - function unknown

Question 17

What does the abnormal HD protein contain?

Answer 17

Increased number of glutamine amino acids = polyglutamine (polyO) expansion which alters protein structure and biochemical properties

Question 18

What are the aggregates in HD?

Answer 18

PolyO cellular protein aggregates - unknown if they cause disease

Question 19

Basal ganglia is affected in HD. Which part of the basal ganglia especially?

Answer 19

Caudate nucleus

Question 20

Anticipation is a phenomenon associated with which type of disorders?

Answer 20

Triplet repeat disorders

Question 21

Why are triplet repeat disorders associated with anticipation?

Answer 21

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

Question 22

The phenomenon of anticipation is often linked to what?

Answer 22

The gender of the parent

Question 23

Huntington disease has high anticipation risk when inherited from whom?

Answer 23

Paternal inheritance

Question 24

Myotonic dystrophy has high anticipation risk when inherited from whom?

Answer 24

Maternal inheritance

Question 25

Fragile X syndrome has high anticipation risk when inherited from whom?

Answer 25

Maternal inheritance

Question 26

What is the mode of inheritance of fragile X syndrome?

Answer 26

XL recessive

Question 27

What is the mode of inheritance of myotonic dystrophy?

Answer 27

AD

Question 28

How is HD triplet repeat size related to age of onset?

Answer 28

The higher the CAG trinucleotide repeat number, the lower the age at neurological onset

Question 29

If somebody had symptoms of HD, which gene test would be appropriate?

Answer 29

Diagnostic gene test

Question 30

If somebody was asymptomatic for HD, which gene test would be appropriate?

Answer 30

Predictive gene test

Question 31

What is predictive testing?

Answer 31

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

Question 32

In which other diseases (other than HD), is predictive gene testing possible?

Answer 32

- BRCA (familial breast cancer gene) - HNPCC (hereditary non-polyposis colon cancer) - myotonic dystrophy

Question 33

What treatments are available for HD?

Answer 33

- symptomatic treatment only at present - no prevention or cure - testing does not save lives

Question 34

What reasons may be given for wanting HD predictive testing?

Answer 34

- just 'want to know' - plan future care - want to plan their career - make decisions about children - inform other relatives whose risk may change

Question 35

Does HD predictive testing give a certain result?

Answer 35

If negative - complete certainty If positive - certainty as fully penetrant But cannot tell age of onset, course, severity

Question 36

What must be considered when choosing to have HD predictive testing?

Answer 36

- insurance - changing risk to others - impact on current and future relationships - psychological impact - no medical advances yet

Question 37

How many drop out of HD predictive testing?

Answer 37

50-60%