Predisposition to Adult Onset Genetic Disease

Question 1

What are the different mechanisms of adult onset genetic disease?

Answer 1

• Single gene
• Chromosomal
• Mitochondrial
• Multifactorial and environmental (polygenic genetic component interacting with environmental factor)

Question 2

Explain what is meant by genetic/environmental contributions to a disease is a spectrum?

Answer 2

Question 3

What are the 4 principles of medical ethics?

Answer 3

• Respect for autonomy
• Beneficence
• Non-maleficence
• Justice

Question 4

What are the consequences of medical ethics in regards to genetics?

Answer 4

• Test information must be usable for prevention or treatment
• Susceptibility testing requires adequate information about uncertainty
• Predictive testing requires proper counselling
• Third parties (employers, insurers) should have no access

Question 5

What is the aetiology of amyotophic lateral sclerosis (ALS)?

Answer 5

• 5-10% familial
• Not complete penetrance, can have mutation and not phenotype

Question 6

Describe the aetiology of ALS (incidence, age)?

Answer 6

• 1-2/100,000
• Mean age onset 55 (younger in familial form)

Question 7

What does ALS stand for?

Answer 7

Amyotrophic lateral sclerosis

Question 8

What are clinical features?

Answer 8

• Progressive muscle weakness, wasting and increased reflexes (UMN and LMN signs)
  
  • Limb and bulbar muscles involved
• Pure motor signs with fasciculations
• Cognition spared
• Increased Cu/Zn superoxide dismutase (SOD)
  
  • SOD protects cells from free radical damage as well as DNA damage, lipid peroxidation, ionising radiation, protein denaturation
  • 3 forms – SOD1 in cytoplasm, SOD2 in mitochondria, SOD3 is extracellular
  • Genes located on chromosomes 21,6 and 4

Question 9

What does SOD stand for?

Answer 9

Superoxide dismutase

Question 10

What is SOD?

Answer 10

• SOD protects cells from free radical damage as well as DNA damage, lipid peroxidation, ionising radiation, protein denaturation
• 3 forms – SOD1 in cytoplasm, SOD2 in mitochondria, SOD3 is extracellular
• Genes located on chromosomes 21,6 and 4

Question 11

Describe the management for ALS?

Answer 11

• No cure and no satisfactory treatment
• Non-invasive ventilation

Question 12

What is a complication of ALS?

Answer 12

• Death due to respiratory failure

Question 13

What is the aetiology of Huntington’s disease?

Answer 13

• Unique mutation causes – CAG expansion
• Fully penetrant

Question 14

Describe the epidemiology of Huntington’s disease (age)?

Answer 14

Adult onset

Question 15

What are the clinical features of Huntington’s disease?

Answer 15

• Movement disorder
  
  • Chorea (involuntary, irregular, unpredictable movements)
  • Athetosis (slow, involuntary, convulated movement of fingers, hands, toes and feet, in some cases arms, legs, neck and tongue)
  • Myoclonus (quick, involuntary muscle jerk)
  • Rigidity
• Cognitive changes
  
  • Poor memory and planning
  • Subcortical dementia (executive function)
    
    • NOT classic dementia
• Personality change
  
  • Irritable
  • Apathetic
  • Loss of empathy
  • Disinhibition
  • Self-centred
• Psychiatric disease
  
  • Depression
  • Paranoia
  • Psychosis

Question 16

What is choera?

Answer 16

• Chorea (involuntary, irregular, unpredictable movements)

Question 17

What is athetosis?

Answer 17

• Athetosis (slow, involuntary, convulated movement of fingers, hands, toes and feet, in some cases arms, legs, neck and tongue)

Question 18

What is myoclonus?

Answer 18

• Myoclonus (quick, involuntary muscle jerk)

Question 19

Describe the management for Huntington’s disease?

Answer 19

• No cure, unsatisfactory treatments
• Genetic testing
• Supportive care