Prenatal Diagnosis of Genetic Disease

Question 1

What are the scans offered for a normal pregnancy?

Answer 1

Nuchal scan –10-14 weeks
Mid-trimester anomaly scan
All pregnant women should be offered ultrasound scans at 20-22 weeks as well

Question 2

When is a nuchal scan offered and what is it used to determine?

Answer 2

12 weeks 
Date the pregnancy
Multiple pregnancies 
Major foetal abnormalities 
Early miscarriage 
Risk of chromosomal abnormalities

Question 3

What is considered an abnormal nuchal translucency and what would such a result suggest?

Answer 3

Greater than 3mm – indicates possibility of: Chromosomal abnormalities
Birth defects
Skeletal dysplasia

Question 4

What are the three types of prenatal testing and which test fall under each category?

Answer 4

Non-invasive (ultrasound, MRI) Minimally invasive (maternal serum screening, cell free foetal DNA) Invasive (chorionic villus sampling, amniocentesis)

Question 5

What can ultrasound tests be used for?

Answer 5

Nuchal translucency
Nasal bone
Dating

Question 6

When is maternal serum screening done?

Answer 6

11-14 weeks AND 16-20 weeks

Question 7

What does maternal serum screening look for?

Answer 7

11-14 weeks = looks for presence of hCG and PAPP A

16-20 weeks = looks for presence of hCG, PAPP A, AFP and uE3

Question 8

In what situation is cell-free foetal DNA testing offered?

Answer 8

Offered in particular if the baby has a chance of having an X-linked condition

Question 9

What is cffDNA used to determine?

Answer 9

The sex of the baby (looks for the presence of the SRY gene)

Question 10

What are the limitations of NIPD and NIPT?

Answer 10

Multiple pregnancies – cannot tell which foetus the DNA is from
High BMI – relative proportions of cffDNA is reduced in obese women Ethical issues

Question 11

What are the benefits of NIPD and NIPT?

Answer 11

No risk of miscarriage Reduces the need for more invasive testing

Question 12

What is the problem with invasive prenatal testing?

Answer 12

Small risk of miscarriage

Question 13

What is CVS and when is it done?

Answer 13

Chorionic villus sampling – take a sample from the chorionic villus which has the same genetic material as the foetus
11-14 weeks

Question 14

What is amniocentesis and when is it done?

Answer 14

Taking a sample of amniotic fluid – 16+ weeks

Question 15

What further tests are done to the DNA obtained via CVS or amniocentesis?

Answer 15

Karyotype QF-PCR (test for trisomies)

Question 16

Describe pre-implantation genetic diagnosis.

Answer 16

IVF is used to produce a zygote
A cell is sampled at the 8-cell stage and tested to identify any genetic defects Only the cells with no genetic defects will be implanted

Question 17

What are the eligibility criteria for PGD?

Answer 17

Female partner is under the age of 40
BMI above 19 and less than 30
No living unaffected children from this relationship
Both partners are non-smokers

Question 18

list the indications for referral to Genetics Services regarding prenatal testing

Answer 18

couple consults genetics services if:

• combined tests show increased risk of downs syndrome OR scans show abnormal eg nuchal translucency
• parents are carriers
• previous pregnancy affected