Prenatal diagnosis of genetic diseases

Question 1

What are the indications for referral to Genetic Services regarding prenatal testing?

Answer 1

• Abnormal findings at nuchal scan(10-14)/mid-trimester scan
• Results of combined tests which gave ↑ risk of DS
• previous pregnancy was affected with a condition (CF, DS)
• parent(s) is a carrier
• Family history of genetic condition

Question 2

Non-invasive prenatal tests

Answer 2

Ultrasound
-Early/dating scans, nuchal translucency and nasal bone(DS)
Maternal serum screening
-markers in blood can detect ↑ risk oftrisomy 21,18 and neural tube defects
cffDNA (cell free fetal DNA)
-analyse DNA fragments in maternal plasma (10-20% comes from placenta)
-X linked conditions
-determine sex
-4-5 (best at 9weeks)

Question 3

What are the benefits of NIPT?

Answer 3

• ↓ invasive tests due to sex determination
• no miscarriage risk
• more comfortable than invasive
• offered earlier and results are earlier

Question 4

What are the limitations of NIPT?

Answer 4

-difficult in multiple pregnancies
>can’t determine which child the DNA is from unless they are identical
-high BMI = more of own cell free DNA = ↓ relative proportion of cffDNA
-Invasive testing may still be needed

Question 5

What can non-invasive pregnancy diagnosis be used for?

Answer 5

Achondroplasia
Thanatophoric Dysplasia
Apert Syndrome

Question 6

Invasive Prenatal tests

Answer 6

Offered when other testing shows a known risk and if there is a family history
CHORIONIC VILLUS SAMPLING (CVS)
-11-14 weeks (1-2% risk of miscarriage)
-Use sample of chorionic villi-part of the placenta (same DNA as the foetus)
-Transabdominal or transvaginal
AMNIOCENTESIS
-From 16 weeks
-amniotic fluid contains foetal cells
-1% risk of miscarriage, infection and Rh sensitisation

Question 7

What are some reproductive options?

Answer 7

-Conceive naturally
>no prenatal testing
>have prenatal testing
-Egg/sperm donors
-Adoption
-Choose not to have children
-Pre-implantation Genetic Diagnosis

Question 8

Egg and sperm donation

Answer 8

• Children can contact the donor at 18
• Through UK HFEA licenced fertility centre (conform to medical, ethical and legal standards)
• can find private donors
• Can consider going abroad

Question 9

Adoption

Answer 9

1. Registration and checks (medical and criminal background check, 3 written references)
2. Assessment and approval (home visits)
3. Search for a child begins

Question 10

Pre-implantation Genetic Diagnosis

Answer 10

IVF + genetic testing before the implantation
FEMALE:
-under 40
-BMI between 19 and 30
BOTH are non smokers
-funded for 3 rounds

Question 11

Problems associated with PGD

Answer 11

• Emotional and physical implications
• Long process
• 30% success rate per cycle, 40% per embryo transfer
• Used for translocation carriers, HD, Duchenne muscular dystrophy and CF

Question 12

What is the role of genetic counselling in prenatal testing?

Answer 12

Arrange and explain the different tests
Facilitate decision making
Give results
Arrange termination if necessary
Discuss risks and plans for future pregnancies

Question 13

Factors facilitating decision making

Answer 13

• Previous experience
• Family situation
• Religion
• personal belief
• psychosocial situation
• Couple may not agree

Question 14

Outline the PGD process

Answer 14

1. Stimulate ovaries
2. collect eggs
3. Insemination
4. Fertilisation
5. Embryo Biopsy (once 8 cells in size, a cell is removed)
6. Embryo testing
7. Embryo transfer ( max of 2, don’t have condition or are carriers are considered)
8. Pregnancy test