25 - Cystic Fibrosis

Question 1

What was the first country to get all new borns to have natal screening

Answer 1

New Zealand

Whole country screened

Question 2

What does the newborn screening program include?

Answer 2

Heel Prick
20 metabolic disorders tested
If this screen is positive parents will often google and get lots of often false information which scares and confuses them

Question 3

Cystic Fibrosis

Answer 3

• CFTR gene > CFTR protein folds and sits in the membrane to form a Cl- channel
• in CF Cl- can’t be transported out of the cell, Na and water accumulate in the cell, lumen contents in gut and airways become viscous and sticky

Question 4

Is there a cure for CF

Answer 4

no only symptomatic treatment. Early diagnosis better outcome hence screening

Question 5

What complications can CF cause

Answer 5

• pancreatic insufficiency and chest infections (thick secretions block the duct)
• can’t digest food so weight loss
• no release of enzymes so are reabsorbed into the blood > basis of screening!

Question 6

What is the screening test for CF

Answer 6

1. High blood trypsin
2. If high then 3 common CF genes tested for
   (top 1% tested for)

Question 7

WHat if the screening CF test is positive

Answer 7

• leter to midwife

- hard as thought baby was healthy and are excited

Question 8

What could a positive CF screen mean?

Answer 8

• has CF

- is a carrier

Question 9

What would the family want to know

Answer 9

• is he a carrier or does he have the disease
• what does a positive screen mean
• what are the symptoms?
• is it a mistake?
• what about other children?
• what is CF?
• will he die?
• what are his chances of having CF
• can it be treated?

Question 10

What are the next steps after a positive screen test?

Answer 10

1. Sweat Test (salty)
2. Genetics (confirmation)
3. Stool sample for enzymes (NO chymotrypsin)

Question 11

What does it mean for the child? What symptoms will he show?

Answer 11

1. Most commonly show recurrent pneumonias leading to progressive lung disease
2. Failure to thrive
   - other complications due to thick secretions and poor secretion and absorption

Question 12

What is the initial management of CF?

Answer 12

Regular reviews of CF patients are done

1. History
2. Growth
3. Physical examination
   - cough
   - chest deformity
   - auscultation
   - abdominal exam

Question 13

Investigations done during regular reviews for CF patients

Answer 13

1. Check for infection (throat swab, cough suction, sputum)
2. O2 monitoring
3. Lung function testing
4. Imaging

Question 14

Infection?

Answer 14

Need to check regularly
Most common causes of infection are staph aureus and something else
Infection rates and the types of bacteria involved change over time so need to know what you’re looking for?

Question 15

What are the 3 main treatments for CF?

Answer 15

1. Respiratory (physiotherapy and exercise)
2. Nutrition
3. Other - specific gene therapies

Question 16

Respiratory treatment

Answer 16

1. Chest physio
2. Exercise
3. Antibiotics

Question 17

Nutrition treatment

Answer 17

1. Enzyme replacement
   - enable food absorption
2. Vitamin supplements
3. Salt supplements
4. High calorie diet
5. Nutritional supplements
6. Gastrostomy feeds

Question 18

How many CF mutations are there

Answer 18

7 main types

Question 19

Why is knowing the specific mutation in each CF case important?

Answer 19

• helps with treatment and predicts severity and symptoms
• drugs/gene therapies being developed to target each defect separately as each cause an different abnormality in the protein

Question 20

For what mutation do they have good specific treatment for

Answer 20

3
no symptoms after treatment
But not funded in NZ
Only 5% of cases

Question 21

How long do CF patients live?

Answer 21

40-50 years

Question 22

Clinical geneticist vs genetic counsellor

Answer 22

1. medical doctor - makes the diagnosis and discusses

2. relevant degree - meet with the extended family after the diagnosis

Question 23

What is genetic counselling

Answer 23

Genetic counselling is a communication process which aims to help individuals, couples and families understand and adapt to the medical, social, reproductive, psychological and familial implications of the genetic aspect to specific health conditions

Question 24

What are things you need to consider with genetic testing?

Answer 24

• inadvertently revealing family relationships (dad doesn’t carry the mutation or lab mix up)
• Need to gain informed consent for testing
• to test children we have to be able to demonstrate a direct benefit
• discuss who can have access to the results (hopefully wider family so can access accurate genetic testing)
• distress over the diagnosis (loss of perfect child)
• feelings of guilt
• options for the future i.e. will the parents be able to work?

Question 25

When they ask about risk

Answer 25

construct a pedigree - risk to other family members

Question 26

Family planning

Answer 26

- give support in making difficult and distressing decisions

Question 27

What are family planning options you would give?

Answer 27

- not having further children - having children with no prenatal testing of the child - sperm or egg donor - prenatal testing (can prepare or terminate) - PGD with IVF

Question 28

What are family planning decisions influenced by

Answer 28

Ethical and religious beliefs, views on sickness and disability, treatment availability, availability of social and financial support > whatever the case is or what they decide on you need to support the decision that is best for that family at that time

Question 29

CVS

Answer 29

- 11-13 weeks - test placental tissue - done at MFM units - need maternal sample - can get placental Mosaicsm - results take 1-2 weeks - 1/500 risk - reveals the karyotype and gender

Question 30

Amnio

Answer 30

- 15 weeks + - testing amniotic fluid - results longer - risk higher - gender and karyotype

Question 31

PGD

Answer 31

``` Pre-Implantatation Genetic Diagnosis - couples who are eligible can access up to 2 publically funded cycles ELIGIBLE: - female under 40 - non-smoker - BMI under 32 - less than 2 affected kids - expensive - uses ICSI ```

Question 32

ICSI?

Answer 32

Intracytoplasmic Sperm injection

Question 33

Is pregnancy garanteed from PGD

Answer 33

NO - 30% success rate - may get no eggs from mother - no reliable embryo - may not survive the freeze - not every embryo is suitable for biopsy - genetic test may be inconclusive (so do diagnostic test on fetus) - may not be any unaffected embryo - doesn't rule out chromosome abnormalities!

Question 34

If a couple wants to test their baby what do we have to consider

Answer 34

- that they know what they are getting into

Question 35

Why may you do a test?

Answer 35

- previously affected pregnancy - family history - parents are known carriers - abnormality on scan/screening - parental concern (would screen first) In the future may be due to .. - parents KNOW their genotype - NIPT (maternal serum with fetal DNA) - stem cell therapy for affected fetuses?

Question 36

What does prenatal diagnosis provide?

Answer 36

Informed reproductive CHOICE - impact on family and friends - prevent suffering of baby - reassurance - options not to continue if baby is affected - prepare for new baby

Question 37

Prenatal diagnosis

Answer 37

Requires fetal dna so is invasive (placenta or amniotic) DONT need blood There is evidence we can get this from maternal plasma/serum Can get from embryo at IVF or PGD

Question 38

NIPT

Answer 38

Non-invasive Prenatal testing - fetal DNA in maternal plasma and serum - sequence the 10 most common mutations - no risk - simpler and less stressful - earlier result