Genetics

Question 1

Mean age of onset of Amyotrophic lateral sclerosis

(Motor neurone disease)?

Answer 1

Mean age onset 55yrs (younger in familial forms)

Question 2

Familial rate of of Amyotrophic lateral sclerosis

(Motor neurone disease)?

Answer 2

5-10% are familial

Question 3

Clinical features of Amyotrophic lateral sclerosis

(Motor neurone disease)?

Answer 3

Progressive muscle weakness, wasting and increased reflexes
(ie upper and lower neurone signs)

Limb and bulbar muscles involved

Pure motor signs (with fasciculations)

Cognition spared

Death due to respiratory failure

Question 4

Which enzyme is affected in Amyotrophic lateral sclerosis

(Motor neurone disease)?

Answer 4

Cu/Zn superoxide dismutase (SOD) - catalyses conversion of intracellular superoxide radicals produced during normal metabolism

In humans, three forms of superoxide dismutase are present:

1) SOD1 is located in the cytoplasm
2) SOD2 in the mitochondria
3) SOD3 is extracellular

Question 5

Role of SOD (Superoxide dismutase)?

Answer 5

The presence of SOD protects many types of cells from free radical damage that is important in ageing and ischaemic tissue damage

SOD also helps protect cells from DNA damage, lipid peroxidation, ionising radiation damage, protein denaturation
………….. and other forms of progressive cell degradation

Question 6

Huntingtons disease clinical features?

Answer 6

> Movement Disorder = chorea, athetosis, myoclonus, rigidity

> Cognitive changes

• poor planning & memory
• subcortical dementia (executive function)
• NOT classical dementia

> Personality change

• Irritable
• Apathetic
• Loss of empathy
• Disinhibition
• Self centred

> Psychiatric disease

• Depression
• Paranoia
• Psychosis

Question 7

Mode of inheritance of Huntington’s?

Answer 7

Autosomal dominant

Question 8

If there is high penetrance of a disease what is the advantages of predictive testing?

Answer 8

Uncertainty of gene status removed.

If negative:
- Concerns about self and offspring reduced.

If positive:

• Make plans for the future
• Arrange surveillance/ treatment if any
• Inform children/decide whether to have children.

Question 9

If there is high penetrance of a disease what is the disadvantages of predictive testing?

Answer 9

If positive:

• Removes hope
• Continues uncertainty (when)
• Known risk to offspring
• Impact on self / partner / family / friends
• Potential problems with insurance / mortgage.
• Problems with employers, schools etc

If negative:

• Expectations of a ‘good’ result
• ‘survivor’ guilt.

Question 10

Principles of Ethics in Medicine?

Answer 10

Respect for autonomy
Beneficence
Non-maleficence
Justice

Question 11

When should children or adolescents be screened for genetic disease?

Answer 11

Once tested if there are potential medical benefits