Lecture 18- Testing for genetic disorders Flashcards
Purpose of Prenatal testing and screening
Often done if there is a concern of risk
Guides families in decisions around the pregnancy
-potential termination?
-Medical & psychological support
What is Prenatal Testing?
Screening tests and diagnostic test
Difference between screening and diagnostic tests
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
What are the clinical indications to do prenatal testing for Chromosomal or single gene disorders
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
Screening Stratagies
- Ultrasound scan of pregnancy
- Nuchal Translucency
- Maternal Serum Testing
Screening Ultrasound
8 wks : check dates, confirm # babies
18wks: detailed scan of anomalies can be done
Safe, no risk to mother or fetus
Nuchal Translucency
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)
Maternal Serum Testing
Blood test
Performed ~15-17 wks
-testing for 2-4 feto-placental proteins1
Risk prediction for Down syndrome
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%
Types of Diagnostic Tests
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)
Chorionic Villus Sampling
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
Amniocentesis
15-16wks
Needle injected into uterus, collects amniotic fluid that contains fetal cells
-may need to culture cells before analysis
-Miscarriage risk ~1%
NEW SCREENING TEST
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%
Issues with new screening test
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
Benefits when testing prenatal testing
Reassurance when results are normal
Advance warning for medical team
psychological preparation for babies arrival
-info, is termination an option?