Condition- Huntington's disease

Question 1

Describe the inheritance of Huntington’s Disease

Answer 1

Autosomal Dominant

Question 2

In huntington’s disease there is a defect on which chormosome and in which gene? And what is this defect?

Answer 2

• Chr 4 in the Huntingtin gene
• Repeat expansion of CAG trinucleotide

Question 3

What impacts the age of onset of Huntington’s Disease?

Answer 3

Number of CAG repeats- the greater the number of repeats the earlier the onset of presentation

Question 4

Huntington’s disease is said to show a phenomenon of anticipation. What does this mean?

Answer 4

As the CAG repeat is passed down generations- there is a greater opportunity for a CAG repeat to occur. So more CAG repeats occur as it goes down the generation. Meaning age of onset becomes earlier down each generations

Question 5

What effect does this mutation in the Huntingtin gene have on the brain?

Answer 5

• Excess deposition of toxic proteins
• Degradation of cholinergic and GABAergic neurones in the caudate and putamen of the brain (striatum of the basal ganglia)
  
  • This is important in inhibition of movement

Question 6

List some of the typical signs and symptoms of Huntington’s disease…

Answer 6

• Movement Problems:
  
  • Chroea
  • Athetesis- snake-like hand movements
  • dystonia
  • saccadic eye movements
• Personality changes:
  
  • irritability
  • apathy
  • depression
  • dementia
  • intellectual impairment
    *

Question 7

List some of the signs of Huntington’s disease on clinical examination

Answer 7

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

Question 8

List some investigations you could conduct to confirm whether a patient has Huntingtin’s disease

Answer 8

• Genetic Analysis
  
  • Diagnostic if there are > 39 CAG repeats in the HD gene
  • Reduced penetrance leads to an intermediate number of CAG repeats
• Imaging- Brain MRI/CT
• Bloods- To exclude other pathology

Question 9

What might be seen on an MRI/CT Brain of a patient with Huntington’s disease

Answer 9

Brain MRI or CT may show symmetrical atrophy of the striatum and butterfly dilation of the lateral ventricles

Question 10

How many CAG repeats are required to conclude that a patient has Huntingtons disease?

Answer 10

>39 CAG repeats