Genetics 5 - Prenatal Screening

Question 1

What process happens in a normal pregnancy?

Answer 1

• Positive pregnancy test
• Booked onto antenatal care
• Nuchal scan
• Mid-trimester anomaly scan
• Ultrasound examination at 11-14 weeks and 20-22 weeks

Question 2

What are the aims of the 12 week nuchal scan?

Answer 2

• Date the pregnancy
• Diagnose multiple pregnancy
• Diagnose major fetal abnormalities
• Diagnose early miscarriage
• Assess down syndrome risk

Question 3

How is down syndrome risk determined in the nuchal scan?

Answer 3

This takes into account the:

• Maternal age
• Blood hormone levels
• Nuchal translucency thickness (>3mm)
• Blood flow through the heart
• Nasal bone

Question 4

When is prenatal testing arranged?

Answer 4

• Following an abnormal scan
• Following results of a combined test which give an increased risk of down syndrome
• If the previous pregnancy is affected with a condition
• If parents are carriers

Question 5

What arw the aims of prenatal testing?

Answer 5

• Inform and prepare parents for birth of an affected baby
• Allow in utero treatment
• Manage the remainder of the pregnancy
• Prepare for complications after birth
• Allow termination of an affected fetus

Question 6

What are the three types of prenatal tests?

Answer 6

• Scanning (ultrasound or MRI)
• Non-invasive (blood test, cell free fetal DNA)
• Invasive (choronic villus sampling/amniocentesis)

Question 7

What does a high level/anomaly scan do?

Answer 7

This looks at the fetal face at around 18-20 weeks, identifying factors such as a cleft lip.

Question 8

What does a maternal serum screening look for?

Answer 8

• Looks for maternal serum markers in the blood that detect increased risk of fetal trisomy 21, 18 or neural tube defects
• 1st trimester is performed with a nuchal translucency measurement, looks at hCG and PAPP A
• 2nd trimester looks at AFP, uE3, hCG

Question 9

How is cell free fetal DNA gathered and tested?

Answer 9

• DNA fragments in the maternal plasma are tested.

- Fetal DNA comes from the placenta, though most of the DNA in the plasma is maternal.

Question 10

When is cell free fetal DNA detected?

Answer 10

Detectable at 4-5 weeks gestation, accurately detected at 9 weeks

Question 11

How can trisomy 21 be identified using cell free fetal DNA?

Answer 11

The amount of cfDNA for chromosome 21 is higher than in normal pregnancies.

Question 12

What diseases is the maternal blood test used to detect?

Answer 12

• Achindroplasia
• Thanatophoric dysplasia
• Apert syndrome
• Offered when there is an X-linked condition in the family as the SRY gene can be detected to determine if invasive tests are needed.

Question 13

Where is cffDNA used to test for aneuploidy?

Answer 13

It is offered privately (Harmony)

Question 14

What are the limitations of non-invasive prenatal diagnosis?

Answer 14

• If there are multiple pregnancies you cant tell which fetus DNA is from
• Women with a high BMI have a lower proportion of cell-free fetal DNA
• An invasive test is still required to confirm an abnormal result.

Question 15

What are the benefits of non-invasive prenatal diagnosis?

Answer 15

• The number of invasive tests carried out are reduced,
• No increased risk of miscarriage
• Less expertise is required to carry out a blood test than an invasive test
• Offered earlier than traditional invasive testing, so results are gathered earlier.

Question 16

What is choronic villus sampling?

Answer 16

• Occurs at 11-14 weeks, may be transabdomina, or transvaginal.
• It takes a sample of the choronic villi, a part of the developing placenta, which has the same DNA as the fetus.
• Uses ultrasound guidance

Question 17

What is aminocentesis?

Answer 17

• Occurs from 16 weeks
• It takes a sample of amniotic fluid containing fetal cells
• Uses ultrasound guidance

Question 18

What are the risks of aminocentesis?

Answer 18

• Up to 1% risk of miscarriage
• Infection
• Rh sensitisation

Question 19

What are the risks of choronic villus sampling?

Answer 19

It has a 1-2% risk of miscarriage

Question 20

What tests are done with the DNA sample?

Answer 20

• The genetic disorder in question is tested
• Karyotype is tested if necessary, with results within 2 weeks
• QF-PCR is used to look for translocations

Question 21

What are the reproductive options where there is a known reproductive risk?

Answer 21

Patients may

• Concieve naturally with/without prenatal testing
• Use an egg or sperm donor
• Adopt
• Choose not to have children
• Use pre-implantation genetic diagnosis.

Question 22

What are the stages of adoption?

Answer 22

• Registration and checks takes around 2 months, 3 written references are required
• Assessment and approval involves home visits by a social worker, and a panel interview. Takes around 4 months

Question 23

Describe the process of PGD

Answer 23

• After hyperstimulation of the ovaries, many eggs are collected and surrounded by sperm to allow fertilisation
• There may be an intracytoplasmic sperm injection in conditions caused by a single faulty gene to reduce risk of a wrong diagnosis.
• An embryo biopsy occurs at the 8 cell stage
• The embryo can then be transfered to the womb

Question 24

For what disorders is PGD used?

Answer 24

• Translocation carriers
• Huntingtons Disease
• Duchenne muscular dystrophy
• CF

Question 25

List the eligability criteria for PGD.

Answer 25

• Female partner under 39, BMI 19-30
• Both partners dont smoke
• Couple are in a stable relationship, living together with no unaffected children
• Risk at least 10%
• No accurate genetic test available
• No welfare concerns
• Female partner has good hormone levels, suggesting it will work

Question 26

What is the role of genetic councelers in prenatal testing?

Answer 26

• Arrange and explain procedures
• Give results of tests
• Arrange termination
• Discuss risks in future pregnancies
• Facilitate decision making (may be different religions, personal beliefs, and indecision)