Huntington's

Question 1

define Huntington’s disease?

Answer 1

autosomal dominant trinucleotide repeat disease ( CAG repeat on chromosome 4 )

slowly progressive, neurodegenerative disorder characterised by chorea, incoordination, cognitive decline, personality changes, and psychiatric symptoms, culminating in immobility, mutism, and inanition

Question 2

state a typical presentation of huntington’s disease?

Answer 2

Random jerky movements throughout the day, FHx, mood changes/ lack of concentration/ etc

Question 3

outline the aetiology of huntington’s disease?”

Answer 3

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

Causes atrophy and neuronal loss of striatum and cortex

Autosomal DOMINANT

Earlier age of onset with each successive generation

Question 4

summarise the epidemiology of Huntington’s disease?

Answer 4

Average age of onset: 30-50 yrs

Question 5

what are the risk factors for huntington’s disease?

Answer 5

CAG repeats

Family history

Question 6

what are the presenting symptoms of huntington’s disease?

Answer 6

Family history

INSIDIOUS onset in middle-age

Progressive

EARLY MILD SYMPTOMS:

• Lability (exaggerated changes in moods e.g. uncontrollable laughing/crying)
• personality change
• impaired work or school performance
• Dysphoria (a state of unease or generalised dissatisfaction with life)
• Irritability + impulsivity
• Incoordination
• Fidgeting
• Clumsiness
• Anxiety

LATER STAGES:

• Rigid
• Involuntary, jerky, dyskinetic movements often accompanied by grunting and dysarthria – CHOREA –> athetosis (writhing movements of hands)
• Dementia
• Fits
• Akinetic
• Lack of concentration
• Bed-bound
• Death

Question 7

what are the signs of huntington’s disease on physical examination?

Answer 7

Chorea

Dysarthria

Slow voluntary saccades

Parkinsonism (tremor, bradykinesia, rigidity + postural instability)

Dystonia (muscles contract uncontrollably)

MMSE shows cognitive and emotional deficits

Question 8

what are the appropriate investigations for huntington’s disease?

Answer 8

Diagnosis is clinical initially

Genetic Analysis

• Diagnostic if there are > 40 CAG repeats in the HD gene
• <28 repeats is norm
• 29 – 35 repeats could happen in their offspring
• 36 – 39 repeats – may or may not develop it in their lifetime
• Reduced penetrance leads to an intermediate number of CAG repeats

Imaging

Brain MRI or CT may show caudate or striatal atrophy-> not specific also seen in other diseases ( neuroacanthocytosis)