An autosomal dominant neurodegenerative disorder

Often presents in mid-life (30-50), but may appear at any age

Aetiology

Huntington’s occurs with expansions of the CAG repeat length at the N-terminal end of the huntington gene (genetic mutation in the huntington gene on chromosome 4)

• All patients with >40 CAG repeats develop Huntington’s disease if they live a normal lifespan.
  • The longer the repeat length the earlier the Sx appear
• Patients with repeats in the 36 to 39 range may develop symptoms of Huntington's disease or may remain asymptomatic.
• Anticipation: The tendency for expansion of the CAG repeat in successive generations (anticipation) puts offspring at risk for earlier onset and increased severity of the disease than their parents.

Pathophysiology

Huntington’s results in degeneration of GABAergic cells and dysfunction of cholinergic pathways in the striatum, particularly the caudate nucleus.

As the neuronal connections between the striatum and GPE are dysfunctional (in the basal ganglia circuitry), there is overactivity of the direct pathway = hyperkinetic disorder

PC

Presents with insidious, progressive worsening of the symptoms. It typically begins with cognitic, psychiatric or mood problems, followed by development of movement disorders.

Movement disorders:

• Chorea (involuntary, irregular, random dance like flowing movements)
• Twitching or restlesness
• Loss of coordination
• Deficit in fine motor coordination
• Slowed saccadic eye movements