Huntington Disease and Predictive testing

Question 1

What is Huntington disease?

Answer 1

Progressive neurodegenerative disorder with motor, cognitive, and psychiatric disturbances - movements

• memory
• mood

Question 2

What movement abnormalities are seen in Huntington disease?

Answer 2

Chorea

Dystonia

Bradykinesia

Swallowing/choking

Dysarthria

Question 3

What mood abnormalities are seen in individuals with Huntington disease?

Answer 3

Depression

Euphoria

Apathy

Anxiety

Aggression

Psychotic symptoms

Question 4

What cognitive deficits are seen in Huntington disease?

Answer 4

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

Question 5

What is the mean age of onset for Huntington disease?

Answer 5

35-44 (range 2-80)

Question 6

What is the median survival time after onset?

Answer 6

15-18 years

Question 7

What type of genetic disorder is Huntington disease?

Answer 7

Autosomal dominant

Question 8

What kind of penetrance does the condition have?

Answer 8

Complete

Question 9

Which gene is responsible for the condition?

Answer 9

HTT gene at 4q16.3

Question 10

What are the characteristics of the normal HTT gene.

Answer 10

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

Question 11

What are the characteristics of the mutant HTT gene?

Answer 11

The HD mutation = an expansion of CAG repeats ≥ 40 repeats

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

Question 12

What is the function of the normal Huntington protein?

Answer 12

Widely expressed in many tissues - function unknown.

Question 13

What is the result of the polyglutamine repeat expansion?

Answer 13

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).

Basal ganglia, especially caudate nucleus primarily affected.

Question 14

What is anticipation and why does it occur?

Answer 14

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

• A phenomenon associated with triplet repeat disorders
• Triplet repeat expansions are unstable and may increase (occasionally contract) when passed to the next generation
• The phenomenon of anticipation is often linked to the gender of the parent:

Question 15

Which other diseases show anticipation?

Answer 15

Myotonic dystrophy and Fragile X

Question 16

What is predictive testing?

Answer 16

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