Commoner Non-Cancer Genetic Disorders: Part 1

Question 1

Huntington Disease:

1. age of onset? [1]
2. signs & symptoms? [4]
3. mode of inheritance? [2]
4. chromosome length is prone to expansion during meiosis, especially if it is inherited from which parent? [1]

Answer 1

1. onset between 30-50yrs
2. signs & symptoms
   
   • progressive chorea (involuntary movements)
   • dementia
   • psychiatric symptoms
   • often underweight due to chorea and difficulty eating
3. autosomal dominant with genetic anticipation
4. prone to expansion, especially if inherited from the father

Question 2

Myotonic Dystrophy:

1. signs & symptoms [3]
2. what is myotonia? [2]
3. what conditions are people with myotonic dystrophy more prone to? [2]
4. mode of inheritance? [2]
5. patient affected after how many repeats? [1]
6. chromosome length is prone to expansion during meiosis, especially if it is inherited from which parent? [1]

Answer 2

1. signs & symptoms
   
   • progressive muscle weakness in early adulthood
   • myotonia
   • cataracts
2. myotonia = disorder of muscle fibres that results in abnormally prolonged contractions so the patient has difficulty in relaxing a movement
3. more prone to:
   
   • diabetes
   • general cardiac defects
4. autosomal dominant with genetic anticipation
5. patient affected after 50 or more repeats
6. prone to expansion especially if inherited from father

Question 3

Cystic Fibrosis

1. signs & symptoms [2]
2. mode of inheritance [1]
3. carrier frequency? [2]
4. pathogenesis of CF? [4]
5. how is CF screened for in new-borns and how is it confirmed? [3]

Answer 3

1. signs & symptoms:
   
   • recurrent lung infections
   • exocrine pancreatic insufficiency (85-90% of cases)
2. autosomal recessive
3. 1 in 20 - 1 in 25 carrier frequency
4. pathogenesis:
   
   • CFTR gene mutation
     
     • prevents normal protein folding and insertion into the plasma membrane
       
       • results in defective chloride ion channel
         
         • leads to increased thickness of secretions
5. screening by immunoreactive trypsin (IRT) level
6. confirmation by:
   
   • DNA test (for CF mutations) and/or
   • sweat testing (for increased chloride concentrations)

Question 4

What is cascade screening? [1]

Answer 4

identification of mutations that permits prenatal diagnosis if desired and the subsequent identification of carrier relatives