Predisposition to Adult Onset Disease

Question 1

Why are adults referred to genetics?

Answer 1

Diagnosis
Predictive testing
Carrier testing 
Cascade screening (after one family member is diagnosed)
Family history (including cancer)
foetal loss or recurrent miscarriages

Question 2

Mechanisms of adult onset genetic disease

Answer 2

Single gene
Chromosomal
Mitochondrial
Multifactorial i.e. +environment

Question 3

What is penetrance?

Answer 3

The concept of the person having a genetic variant and the likelihood of getting the disease associated with it

Question 4

Risk estimation of a disease is easier if the disorder is….

Answer 4

Single gene

High penetrance

Question 5

Features of a multifactorial condition

Answer 5

A polygenic genetic component interacting with environmental factors
Risk estimation more difficult
Risk alleles being identified for common / multifactorial disease

Question 6

Ethics in medicine

Answer 6

Respect for autonomy
Beneficence
Non-maleficence
Justice

Question 7

What conditions is the most predictive testing done in?

Answer 7

Huntington’s disease (most common)
Familial cancer syndromes
Cardiac disease

Question 8

Age of onset of motor neurone disease

Answer 8

55 years

Younger in familial forms

Question 9

Genetics of motor neurone disease

Answer 9

generally sporadic

5-10% familial (AD+AR)

Question 10

Presentation of motor neurone disease

Answer 10

Progressive muscle weakness
progressive muscle wasting 
Progressive increased reflexes
BOTH UPPER AND LOWER MOTOR NEURONE SIGNS
limb and bulbar muscles involved
pure motor signs (with fasciculations)
cognition spared 
Death due to respiratory failure

Question 11

Another name for motor neurone disease

Answer 11

Amyotrophic lateral sclerosis

Question 12

A mutation in which gene causes familial motor neurone disease?

Answer 12

Cu/Zu superoxide dismutase (SOD)

Question 13

What does Cu/Zu superoxide dismutase do?

Answer 13

Catalyses conversion of intracellular superoxide radicals produced during normal metabolism
Motor neurones express it highly
So the presence of SOD protects may types of cells from free radical damage that is important in ageing and ischaemic tissue damage
Helps protect cells from DNA damage and other forms of progressive cell degradation

Question 14

Penetrance of Motor neurone disease

Answer 14

Incomplete penetrance

Question 15

Treatment of motor neurone disease

Answer 15

No treatment

No cure

Question 16

Features of huntington’s disease

Answer 16

Autosomal dominant 
Adult onset
- late 30s/40s but variable 
duration 15-20 years  
unique mutation - CAG expansion 
fully penetrant

Question 17

Duration of huntington’s disease

Answer 17

15-20 years

Question 18

Penetrance of Huntington’s disease

Answer 18

Fully penetrant

Question 19

Mutation of Huntington’s disease

Answer 19

CAG expansion

Question 20

Presentation of Huntington’s Disease

Answer 20

Movement disorder
- chorea 
- athetosis 
- myoclonus 
- rigidity 
Cognitive changes 
- poor planning and memory 
- subcortical dementia (executive function) 
- NOT classical dementia
Personality change 
- "a different person"
- irritable 
- apathetic 
- loss of empathy 
- disinhibition 
- self centred 
Psychiatric disease 
- depression
- paranoia 
- psychosis

Question 21

Treatment of Huntington’s disease

Answer 21

No cure
Unsatisfactory treatments
some treatments for psychiatric component of the disease