Huntington's disease & predictive testing

Question 1

Describe Huntington’s Disease

Answer 1

-Progressive neurodegenerative disorder
-Motor, cognitive, psychiatric disturbances
-Mean age onset= 35-44
Median survival= 15-18 years

Question 2

What are the movement disorders of Huntington’s?

Answer 2

• Chorea
• Dystonia
• Bradykinesia
• Swallowing/choking
• Dysarthria

Question 3

What are the mood disorders of Huntington’s?

Answer 3

• Depression
• Euphoria
• Apathy
• Anxiety
• Aggression
• Psychotic symptoms

Question 4

What are the cognitive disorders of Huntington’s?

Answer 4

• Loss of executive functioning
• Rigidity of thought
• Memory loss
• Dementia

Question 5

Describe the genetics of Huntington’s

Answer 5

• Autosomal dominant
• Complete penetrance
• HTT gene at 4q16.3
• Normal HTT gene at exon 1 has CAG trinucleotide repeats
• Mutation = CAG repeats >40

Question 6

What effects are there of an abnormal protein in the HTT gene?

Answer 6

• Inc no. of polyglutamine expansion = alters protein structure & biochemical properties
• Basal ganglia especially caudate nucleus affected

Question 7

What other triplet repeat diseases is anticipation associated with and which parent gives a high risk of this?

Answer 7

• HD = paternal
• Myotonic dystrophy= maternal
• Fragile X= maternal

Question 8

What diseases can predictive gene testing be used for?

Answer 8

• HD
• BRCA=familial breast cancer
• HNPCC= hereditary non-polyposis colon cancer
• Myotonic dystrophy