Adult Disease

Question 1

Why are adults referred?

Answer 1

DIAGNOSIS

PREDICTIVE TESTING

CARRIER TESTING/CASCADE SCREENING

FHx (incl. cancer)

FOETAL LOSS/RECURRENT MISCARRIAGES

Question 2

Mechanisms of Adult Onset Genetic Disease (gene transmission)

Answer 2

• SINGLE GENE
  
  • CHROMOSOMAL
  • MITOCHONDRIAL
  • MULTIFACTORIAL (genes + environment)

Question 3

Prediction + Uncertainty principles

Answer 3

• TEST INFORMATION MUST be USABLE for PREVENTION/Rx
  
  • SUSCEPTIBILITY TESTING REQUIRES ADEQUATE INFORMATION about UNCERTAINTY
  • PREDICTIVE TESTING REQUIRES PROPER COUNSELLING to ensure pt. are properly supported
  • CHILDREN/ADOLESCENTS should ONLY be TESTED if there are POTENTIAL MEDICAL BENEFITS
  • 3RD PARTIES (employers, insurers) should have NO ACCESS

Question 4

Amyotrophic Lateral Sclerosis (MND): genetics

Answer 4

• SPORADIC (generally)
  
  • 5 - 10% FAMILIAL (AD + AR) - Cu/Zn SUPEROXIDE DISMUTASE (SOD) - 20% of familial cases, 2% of all cases; INCOMPLETE PENETRANCE
  • MEAN AGE ONSET = 55 YRS (YOUNGER in FAMILIAL FORMS)

Question 5

Amyotrophic Lateral Sclerosis (MND): presentation

Answer 5

• PROGRESSIVE MUSCLE WEAKNESS, WASTING, INCREASED REFLEXES (UMN + LMN)
  
  • LIMB & BULBAR MUSCLES involved
  • PURE MOTOR SIGNS (w/ FASCICULATIONS)
  • COGNITION SPARED
  • DEATH due to RESPIRATORY FAILURE

Question 6

Amyotrophic Lateral Sclerosis (MND): management

Answer 6

NO CURE + NO SATISFACTORY Rx

Question 7

Huntington’s Disease: genetics

Answer 7

• AUTOSOMAL DOMINANT: UNIQUE MUTATION (CAG EXPANSION) - FULLY PENETRANT
  
  • ADULT ONSET = LATE 30s/EARLY 40s
  • 15 - 20YRS DURATION

Question 8

Huntington’s Disease: presentation

Answer 8

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 9

Huntington’s Disease: management

Answer 9

NO CURE + UNSATISFACTORY Rx

Question 10

Advantages of Predictive Testing

Answer 10

• UNCERTAINTY of GENE STATUS REMOVED
• If -VE = CONCERNS about SELF & OFFSPRING REDUCED
• If +VE = MAKE PLANS for SUTURE
• If +VE = ARRANGE SURVEILLANCE/Rx if any
• If +VE = INFORM CHILDREN/DECIDE WHETHER to HAVE CHILDREN

Question 11

Disadvantages of Predictive Testing

Answer 11

• If +VE = REMOVES HOPE
• If +VE = CONTINUES UNCERTAINTY (as to when disease will present)
• If +VE = KNOWN RISK to OFFSPRING
• If +VE = IMPACT on SELF/PARTNER/FAMILY/FRIENDS
• If +VE = POTENTIAL PROBLEMS w/ INSURANCE/MORTGAGE
• If-VE = EXPECTATIONS of ‘GOOD’ RESULT
• If -VE = SURVIVOR GUILT

Question 12

Risk Estimation

Answer 12

• depends on CONTINUUM of PENETRANCE

SINGLE GENE DISORDERS w/ HIGH PENETRANCE - RISK ESTIMATION EASIER

MULTIFACTORIAL CONDITIONS

	○ POLYGENIC GENETIC COMPONENT INTERACTING w/ ENVIRONMENTAL FACTORS
	○ RISK ESTIMATION MORE DIFFICULT
	○ RISK ALLELES IDENTIFIED for COMMON/MULTIFACTORIAL DISEASE
	○ PREDICTIVE VALUE of EACH is V. SMALL (however, the combination of all these alleles produces the effect of disease risk)