Lecture 18- Testing for genetic disorders

Question 1

Purpose of Prenatal testing and screening

Answer 1

Often done if there is a concern of risk
Guides families in decisions around the pregnancy
-potential termination?
-Medical & psychological support

Question 2

What is Prenatal Testing?

Answer 2

Screening tests and diagnostic test

Question 3

Difference between screening and diagnostic tests

Answer 3

Screening:

• assess RISK but not a definitive diagnostic test
• non-invasive, low risk
  eg) maternal serum testing for downs syndrome

Diagnostic Tests

• Test for specific chromosomal or genetic abnormality (usually via fetal cells/ DNA)
• invasive test, carries some risk
  eg) gene mutation analysis for cystic fibrosis

Question 4

What are the clinical indications to do prenatal testing for Chromosomal or single gene disorders

Answer 4

Single Gene disorders:
-family history
-one parent has AD disorder
-if both parents carriers 
-X linked
(risk prediction done from analysis of pedigree, may lead to specific diagnostic test).

Chromosomal Disorders

• older mother pregnant
• previous child with significant disorder
• chemical/toxic disorders
• Abnormal screening test result

Question 5

Screening Stratagies

Answer 5

• Ultrasound scan of pregnancy
• Nuchal Translucency
• Maternal Serum Testing

Question 6

Screening Ultrasound

Answer 6

8 wks : check dates, confirm # babies
18wks: detailed scan of anomalies can be done

Safe, no risk to mother or fetus

Question 7

Nuchal Translucency

Answer 7

collection/thickness of fluid under the skin at the back of your baby’s neck.
Measure by ultrasound ~10-13 wks
Noninvasive test
(combined with maternal serum testing to increase sensitivity and specificity for downs syndrome screening)

Question 8

Maternal Serum Testing

Answer 8

Blood test
Performed ~15-17 wks
-testing for 2-4 feto-placental proteins1

Question 9

Risk prediction for Down syndrome

Answer 9

Screening in 2nd trimester by –maternal age and maternal serum can identify 50-75% trisomy 21 pregnancies with a false + rate of 5%

-Fetal NT in 1st and maternal serum in the 2nd reported a detection rate of 85-90% trisomy 21 with a false + rate of 5%

Question 10

Types of Diagnostic Tests

Answer 10

Access to fetal cells
May lead to specific diagnostic test
1) amniocentesis (weeks to culture)
2) Chronic villus test (hours)

These all take 3-4 days to do this testing

also percutaneous umbilical cord blood sampling
-fetoscopy & umbilical cord blood sampling
(done later, very rare to do, high chance of miscarriage)

Question 11

Chorionic Villus Sampling

Answer 11

cells from developing placenta taken and tested
Preferred as done earlier ~10-12 wks
-obtain part of CV (fetal cells), and analyse chromosomes or DNA
-risk of miscarriage

Question 12

Amniocentesis

Answer 12

15-16wks
Needle injected into uterus, collects amniotic fluid that contains fetal cells
-may need to culture cells before analysis
-Miscarriage risk ~1%

Question 13

NEW SCREENING TEST

Answer 13

cell free fetal DNA in the maternal plasma
-non-invsive screening test for anueploidies
-still have to confirm with a diagnostic test
-Not routinely available in NZ
Detection Rate: 99%
False +: 0.9%

Question 14

Issues with new screening test

Answer 14

Not comrehensive testing

• only for common chromosome disorders
• single gene disorders (need to know mutation)
• risk of error

Risk (small) to fetus

Not all think its morally/ethically acceptable

Question 15

Benefits when testing prenatal testing

Answer 15

Reassurance when results are normal
Advance warning for medical team
psychological preparation for babies arrival
-info, is termination an option?

Question 16

Pre-Impantation Genetic diagnosis (PGD)

Answer 16

Uses IVF and tests for the genetic disorder before fertilised eggs are implanted.

• Eggs fertilised ‘in-vitro’, tested in lab to determine if they are genetically affected.
• Non-affected eggs implanted

Expensive, technically difficult

Question 17

Genetic Counselling

Answer 17

Essential part of the process and car of the patients

-Provide up to date info & support