Huntington's Disease

Question 1

Define Huntington’s disease

Answer 1

Autosomal dominant trinucleotide (CAG) repeat neurodegenerative disease characterized by progressive chorea and dementia, typically commencing in middle age.

Question 2

What are the causes/risk factors of Huntington’s disease?

Answer 2

Huntington’s disease is caused by an expanded CAG (normally 10-35; 36 or more in HD) repeat at the N-terminus of the gene that codes for the huntingtin protein on chromosome 4p. Mutation results in a toxic gain of function.

*The disease exhibits anticipation (earlier age of onset in each successive generation). Inheritance is autosomal dominant.

Question 3

What are the symptoms of Huntington’s disease?

Answer 3

• Family history of HD.
• Insidious onset in middle-age: Progressive fidgeting and clumsiness.
• This develops into involuntary, jerky, dyskinetic movements.
• Grunting and Dysarthria
• Late stages: Patients are rigid, akinetic and bed-bound.
• Cognitive changes leading on to dementia. (First symptoms)

Question 4

What are the signs of Huntington’s disease?

Answer 4

• Chorea and dysarthria.
• Twitching
• Bradykinesia and rigidity
• Mental state examination reveals cognitive and emotional deficits.
• low voluntary saccades and supranuclear gaze restriction.

Question 5

What investigations are carried out for Huntington’s disease?

Answer 5

• genetic analysis - diagnostic if ≥40 CAG repeats in the HD gene; an intermediate result is 36-39 repeats
• imaging - brain MRI or CT may show symmetrical atrophy of the striatum (particularly the caudate nuclei) and butterfly dilation of the lateral ventricles
• bloods - may be necessary to exclude other pathology: caeruloplasmin, ANA, blood film (acanthocytes), TFT, ESR