Huntington's Disease

Question 1

Definition

Answer 1

Autosomal dominant trinucleotide repeat disease characterised by progressive chorea and dementia, typically commencing in middle age

Question 2

Aetiology

Answer 2

• The huntingtin gene codes for a protein called huntingtin
• In the huntingtin gene there is a trinucleotide repeat expansion (CAG) that results in toxic gain of function
• Autosomal DOMINANT
• Earlier age of onset with each successive generation

Question 3

Epidemiology

Answer 3

• Average age of onset: 30-50 yrs

Question 4

Presenting symptoms

Answer 4

• Family history
• INSIDIOUS onset in middle-age
• Progressive
• Fidgeting
• Clumsiness
• Involuntary, jerky, dyskinetic movements often accompanied by grunting and dysarthria

• Enquire about drug history (especially cocaine and anti-psychotics)

Question 5

Presenting symptoms (early cognitive changes)

Answer 5

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

Question 6

Presenting symptoms (late stages)

Answer 6

o Rigid
o Akinetic
o Bed-bound

Question 7

Signs on physical examination

Answer 7

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

Question 8

Investigations

Answer 8

• Genetic Analysis
o Diagnostic if there are > 39 CAG repeats in the HD gene
o Reduced penetrance leads to an intermediate number of CAG repeats

• 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