Huntington Disease

Question 1

Define:

Answer 1

Autosomal dominant trinucleotide repeat disease (CAG repeated on Chr 4) characteristed by chorea + dementia typically at middle-age

Question 2

Aetiology/risk factors:

Answer 2

The Huntingtin gene codes for the huntigtin protein which has extra glutamine due to the extra repeats (36+)

This leads to atrophy of the straitum and cortex

This is an autosomal dominant disease which shows anticipation (newer generations have a younger age of onset)

Question 3

Epidemiology:

Answer 3

Average age of onset is 30-50 years

Question 4

Symptoms of the early disease:

Answer 4

• Family history
• INSIDIOUS onset in middle-age
• Progressive

o	Lability 
o	Dysphoria (a state of unease or generalised dissatisfaction with life) 
o	Irritability
o	Incoordination 
o	Fidgeting 
o	Clumsiness 
o	Mental inflexibility
o	Anxiety
o	Develops into dementia

Question 5

Symptoms of the later disease:

Answer 5

o	Rigid 
o	Involuntary, jerky, dyskinetic movements often accompanied by grunting and dysarthria – CHOREA 
o	Dementia 
o	Fits 
o	Akinetic
o	Bed-bound 
o	Death

Question 6

Signs:

Answer 6

• Chorea
• Dysarthria
• Slow voluntary saccades
• Supranuclear gaze restriction
• Parkinsonism
• Dystonia
• MMSE shows cognitive and emotional deficits

Question 7

Investigations:

Answer 7

• Genetic Analysis
o Diagnostic if there are > 39 CAG repeats in the HD gene

Imaging
o Brain MRI or CT may show symmetrical atrophy of the striatum and butterfly dilation of the lateral ventricles

Bloods
o To exclude other pathology