Genetics - Genetic Testing

Question 1

What happens at 10-14 weeks into the pregnancy?

Answer 1

Nuchal scan

Question 2

What is involved in a nuchal scan?

Answer 2

Variety of blood tests and nuchal translucency tests

Question 3

What do we assess the risk of with a nuchal translucency?

Answer 3

Downs

Question 4

What is the main purpose of a nuchal scan?

Answer 4

Detects for multiple pregnancy
Dates the pregnancy
Detects for early miscarriage
Detects for major foetal abnormalities
Detects for Downs

Question 5

When is the next scan after the nuchal scan?

Answer 5

Mid trimester - 20-22 weeks

Question 6

What is the purpose of a mid trimester anomaly scan?

Answer 6

More detailed normal scan - looks at brain, spinal cord, bones, heart face, kindeys

Question 7

How many conditions do we look for with a mid trimester anomaly scan?

Answer 7

11

Question 8

How do we gauge the risk for Down’s in an NT?

Answer 8

Increased thickness of back of neck (above 3mm)

Question 9

What are we measuring in an NT?

Answer 9

Thickness at back of neck

Question 10

What is NT not used for?

Answer 10

Not diagnostic - screening purposes only

Question 11

When do we arrange pre natal testing?

Answer 11

Following abnormalities on normal scans
Combined risk of Downs
Parents have good reason to arrange e.g. family history

Question 12

What are the main aims of prenatal testing?

Answer 12

Inform parents of affected baby

Prepare for complications before or after birth

Question 13

What does prenatal testing allow for?

Answer 13

Termination of foetus

Management of pregnancy around the disease

Question 14

What can a foetal MRI be used for?

Answer 14

Further testing or clarification

Question 15

What can we use to diagnose any cardiac conditions?

Answer 15

Foetal cardiac scan

Question 16

Aside from NT, what else can we use to detect for the risk of trisomy 21/18 or neural tube defects

Answer 16

Maternal serum testing markers in then blood

Question 17

What is the neural tube

Answer 17

Precursor to CNS

Question 18

What are the two non invasive methods of prenatal testing?

Answer 18

Maternal blood tests

cell free foetal DNA (cffDNA)

Question 19

What is cell free foetal DNA?

Answer 19

Where fragments of foetal DNA are shed from the placenta and enter the mother’s blood stream

Question 20

When is the earliest that cffDNA can be detected in the blood

Answer 20

4-5 weeks

Question 21

Why do we not test for cffDNA at its earliest point that it appears?

Answer 21

Cannot be tested until around 9 weeks when results are most accurate.

Question 22

What is NIPD?

Answer 22

Non invasive prenatal diagnosis

Question 23

What NIPDs can we get from cffDNA?

Answer 23

Achondroplasia
Thanatophoric dysplasia
Apert syndrome

Question 24

What non disease can we use NIPD for?

Answer 24

Sexing - SRY gene on the Y chromosome of boys can be detected

Question 25

How much do NIPD cost?

Answer 25

Free on NHS

Question 26

Can we diagnose with NIPT?

Answer 26

No

Question 27

What do we do if we find anomalies with NIPT?

Answer 27

Arrange invasive testing

Question 28

How are multiple pregnancies a limitation with NIPT/D?

Answer 28

We do not know which child is affected or whether both are affected

Question 29

How is women with a high BMI a limitation with NIPT/D?

Answer 29

They will have overall more of their own cell free DNA in the blood

Question 30

What are some of the benefits of NIPT/D?

Answer 30

Non invasive No risk of miscarriage No specialist required Can be offered earlier than most invasive tests

Question 31

When is invasive testing offered?

Answer 31

When there is a known risk of a disease or there is abnormal results from normal scans/ NIPT

Question 32

What are the two main invasive testing methods?

Answer 32

Chorionic Villus Sampling | Amniocentesis

Question 33

What do invasive tests include?

Answer 33

Include molecules, cytogenic and biochemical tests

Question 34

How is invasive testing offered?

Answer 34

Outpatient bases

Question 35

When is CVS carried out?

Answer 35

11-14 weeks

Question 36

What is the risk of a miscarriage with CVS?

Answer 36

1-2%

Question 37

How is a CVS sample taken?

Answer 37

Sample of chorionic villus is taken via the transvaginal or trans abdominal route

Question 38

What is the main benefit of CVS?

Answer 38

Allows the patient to get earlier results than amniocentesis - important for ToP decisions.

Question 39

What is amniocentesis?

Answer 39

Insertion of a needle into amniotic sac and taking a sample of the fluid

Question 40

When is amniocentesis carried out?

Answer 40

15-16 weeks

Question 41

What is the miscarriage risk of amniocentesis?

Answer 41

up to 1%

Question 42

What is another risk of amniocentesis?

Answer 42

Risk of infection or Rh sensitisation

Question 43

What tests do we carry out with an obtained DNA sample?

Answer 43

* Testing for the disorder in question * Karyotyping * QF-PCR

Question 44

What is the purpose of testing for the disorder in question?

Answer 44

We want to see if the foetus is a carrier or whether they are affected/unaffected

Question 45

What is the purpose of karyotyping?

Answer 45

If parents are affected by translocation, there is a chance that the foetus will also be affected

Question 46

What is the purpose of QF-PCR

Answer 46

Carried out for all - looks for trisomy of 13, 18 and 21

Question 47

What is a CGH array?

Answer 47

Detects imbalances on all of the chromosomes and will be able to detect for micro deletions or duplications

Question 48

When is a CGH array offered?

Answer 48

After anomalies on 20 week scan

Question 49

What happens if abnormalities are shown on a CGH array?

Answer 49

We will test the parents to see if the abnormality is inherited or if the foetus is the first affected family member.

Question 50

What is trio-exome?

Answer 50

Prenatal exome testing

Question 51

What is the exome?

Answer 51

Coding region of a genome

Question 52

What does trio-exome allow us to do?

Answer 52

allows us to look at the baby's exome if there are significant abnormalities

Question 53

What do we sequence in tiro-exome?

Answer 53

Exons not introns

Question 54

When there is a known reproductive risk, what options do parents have?

Answer 54

``` Conceive naturally Use egg/sperm donor Adoption Choose not to have children PGD ```

Question 55

What is PGD?

Answer 55

Pre-implantation genetic diagnosis (IVF with additional step to test embryo before implantation)

Question 56

What is step 1 of PGD?

Answer 56

Stimulation of ovaries

Question 57

What is step 2 of PGD?

Answer 57

Egg collection

Question 58

What is step 3 of PGD?

Answer 58

Insemination in lab

Question 59

What is step 4 of PGD?

Answer 59

Fertilisation

Question 60

What is step 5 of PGD?

Answer 60

Embryo biopsy

Question 61

What is step 6 of PGD?

Answer 61

Embryo testing

Question 62

What is step 7 of PGD?

Answer 62

Embryo transfer (if embryo test is ok)

Question 63

What is step 8 of PGD?

Answer 63

Pregnancy test

Question 64

What is ICSI?

Answer 64

Intracytoplasmic Sperm Injection - avoid complications generate by letting sperm compete for the egg

Question 65

When do we use PGD?

Answer 65

Used for genetic conditions e.g. Huntington's DMD susceptibility.

Question 66

What are some of the criteria for PGD?

Answer 66

Non smokers Stable relationship Mother is maximum 39 years old

Question 67

What may decision making depend upon?

Answer 67

Previous experience Family situation Personal/cultural beliefs