Adult Onset Disease

Question 1

Why can you be referred to genetic clinic

Answer 1

Diagnosis
Predictive testing - need to know penetrance
Carrier testing
Cascade screening after one family member is Dx
FH
Fetal loss / miscarriage

Question 2

What are the mechanics of adult onset disease

Answer 2

Single gene
Chromosomal
Mitochondrial
Multifactorial + environment

Question 3

What are single gene disorders more likely to be

Answer 3

Rare
High penetrance so risk easier
Unifactorial
High recurrence

Question 4

What are multifactorial conditions more likely to be

Answer 4

Polygenetic + environment
Risk more difficult 
Complex genetics
Low recurrence 
More common 
Huge amount of variation

Question 5

What causes amyotrophic lateral sclerosis (motor neurone)

Answer 5

Most sporadic

5-10% = familial

Question 6

What is the penetrance of motor neurone

Answer 6

Incomplete

Question 7

What gene is involved in motor neurone

Answer 7

Cu / Zn superoxide dismutase (SOD) gene highly expressed

Damages nerve cell

Question 8

What is Hungtington’s disease

Answer 8

Autosomal dominant adult onset disease of late 30’s / 40’s

Question 9

What gene causes Huntington’s

Answer 9

CAG expansion

Question 10

What is Huntingtons penetrance

Answer 10

Fully penetrant

Question 11

What are the features of hungtingtons

Answer 11

Movement disorder
- Athetosis
- Chorea
- Myoclonus
- Rigid
Cognitive change - memory + executive function
Personality change - irritable, apathetic, disinhibited
Psychatric - depression, paranoia, psychosis

Question 12

What is penetrance

Answer 12

The proportion of people with genotype that express the phenotype

Question 13

What are the advantages of testing

Answer 13

Uncertainty removed 
If -ve then no concerns
If +ve can plan
Identifies high risk and non-carriers 
Early detection and prevention

Question 14

What are disadvantages of testing

Answer 14

Removes hope
Uncertainty about when disease will strike
Impact on self / partner
Insurance issues
Guilt