Genetic Conditions

Question 1

What is Huntington’s disease

Answer 1

A genetic condition that causes progressive neurological dysfunction

Question 2

What is the inheritance pattern of Huntington’s disease

Answer 2

autosomal dominant

Question 3

What causes Huntington’s disease

Answer 3

It is a trinucleotide repeat disorder caused by an expanded CAG repeat at the N-terminus of the HTT gene, which codes for the huntingtin protein

Question 4

What chromosome is the HTT gene located on

Answer 4

Chromosome 4

Question 5

What protein does CAG code for

Answer 5

Glutamine

Question 6

Explain the pathophysiology of Huntington’s disease

Answer 6

• Elongated polyglutamine tail is cleaved and toxic fragments are generated
• Aggregates form that resist degradation and interfere with a variety of normal cellular function

Question 7

What is the primary affected brain region in Huntington’s disease

Answer 7

Striatum

Question 8

What is the CAG repeat threshold for Huntington’s disease certainty

Answer 8

Individuals with 40 or more CAG repeats are certain to develop Huntington’s disease.

Question 9

What is the relationship between repeat length and symptom onset in Huntington’s disease

Answer 9

The longer the repeat length, the earlier symptoms tend to appear

Question 10

What does 36-39 CAG repeats in Huntington’s disease testing indicate

Answer 10

An intermediate result of 36 to 39 repeats implies that the person may or may not develop symptoms of Huntington’s disease during their lifetime.

Question 11

What does a result of 29-35 CAG repeats indicate in Huntington’s disease testing?

Answer 11

This range represents an expanded CAG repeat that will not cause disease in the patient but could expand enough to cause disease in offspring.

Question 12

What is considered a normal result range for CAG repeats in Huntington’s disease testing

Answer 12

<28 repeats

Question 13

Huntington’s disease displays genetic anticipation. Describe this

Answer 13

The tendency for expansion of the CAG repeat in successive generations puts offspring at risk for earlier onset and increased severity of the disease than their parents.

Question 14

Give 5 clinical manifestations of Huntington’s disease

Answer 14

• Chorea - involuntary, random movements
• Personality change - depression, Irritability and impulsivity
• Cognitive decline
• Deficit in fine motor coordination
• impaired tandem walking

Question 15

Characteristics of juvenile Huntington’s disease

Answer 15

Patients with juvenile Huntington’s disease may not have chorea but may present with rigidity or parkinsonian symptoms.

Question 16

How is Huntington’s diagnosed

Answer 16

Diagnoses is clinical and can be confirmed by CAG repeat testing

Question 17

How is Huntington’s disease managed non-pharmacologically

Answer 17

There are no Tx options for slowing/ stopping disease progression
* Counselling patient and family
* Advanced directive
* Palliative care and MDT

Question 18

Pharmacological interventions for Huntington’s

Answer 18

• Chorea - 1. tetrabenazine, 2. sulpiride
• Antidepressants - 1. citalopram, 2. Sertraline

Question 19

Give 3 late manifestations of Huntington’s disease

Answer 19

• Weight loss
• Dysphagia
• Falls

Question 20

What is the life expectancy for someone with Huntington’s

Answer 20

10-20 years after onset of symptoms

Question 21

What are 2 common causes of death in Huntington’s disease

Answer 21

• Aspiration pneumonia
• Suicide