Huntington's

Question 1

What is Huntington’s?

Answer 1

Hereditary neurodegenerative disorder with progressive chorea

Hyperkinetic, brief, irregular and arrhythmic movements

Question 2

What is chorea?

Answer 2

Neurological disorder characterised by jerky involuntary movements affecting the shoulders, hips and face

Question 3

Epidemiology of Huntington’s

Answer 3

1 in 10,000

• Onset 30-50yrs
• Most common hereditary neurological disorder
• Juvenille Huntington’s can present <20yrs

Question 4

How does juvenille Huntington’s classically present?

Answer 4

Behavioural changes at school

Question 5

Aetiology of Huntington’s

Answer 5

AD inheritance pattern

• Mutation = CAG repeats in the Huntingtin gene
• The more CAG repeats the more severe the disease
• CAG repeats accumulate generation on generation
• Leads to toxic accumulation of protein fragments which disrupt cellular function and loss of nerurones in the caudate nucleus and frontal lobes

Question 6

Which areas of the brain are classically affected in Huntington’s?

Answer 6

Caudate nucleus: leads to loss of inhibition of movement

Frontal and parietal lobes: accounting for cognitive changes

Question 7

How many CAG repeats associated with Huntington’s?

Answer 7

36+

Question 8

Clinical features of Huntington’s

Answer 8

• Chorea
• Cognitive changes: psychosis, personality change
• Hyperkinesis
• Dementia
• Primitve reflexes return e.g.snout reflex (press patients lips and they pout)

Question 9

Presentation of Huntington’s

Answer 9

• Middle aged onset
• Prodromal phase of mild psychotic and behavioural symptoms before chorea (e.g. patient neglecting self care, change in personality, irritable, job loss, marriage breakdown)
• Chorea: uncontrollable limb movements
• Dysarthria, dysphagia and abnormal eye movements are common

Question 10

Diagnosis of Huntington’s

Answer 10

If patients have symptoms + FHx the diagnosis is clinical

*Important to consider drug induced symptoms: Levodopa, neuroleptics, amphetamines, antihistamines, tricyclic antidepressants, anticonvulsants, cocaine, oral contraceptives are among the many medications known to cause chorea

Question 11

Investigations for Huntington’s

Answer 11

Bloods: genetic testing

Imaging: MRI showing selective atrophy of head of caudate and increased size of frontal horns of lateral ventricles

*Imaging usually normal in early stages so not really useful for diagnosis*

Question 12

Predictive testing for Huntington’s

Answer 12

Blood sample to assess CAG repeats

<26 repeats = normal

27-35: normal but risk in future generations

36-39: abnormal but person may not be affected

>40: abnormal

Question 13

Management of Huntington’s

Answer 13

No disease modifying drugs are available

Treatment is supportive

Tetrabenzine for hyperkinesis - breakds down dopamine pre-cursors

Severe bradykinesia can occur in childhoof cases: levodopa

SSRIs for depression

Antipsychotics

Question 14

Prognosis in Huntington’s

Answer 14

Progressive neurodegeneration

Death usually due to illness e.g. pneumonia

Suicide is 2nd most common cause of death