Lecture 8: Prenatal Genetics Flashcards
What are the objectives of prenatal diagnosis (three)?
- Provide information to prospective parents about fetal diagnosis.
- Counsel and support prospective parents on reproductive decisions.
- Potentially offer fetal therapy, and ideally, precent pos-natal medical complications.
What are the weeks of each trimester?
1st Trimester:
Weeks 1-13
2nd Trimester:
Weeks 14-26
3rd Trimester:
Weeks 27 - 40
NIPT
Non-invasive prenatal tests/testing
What are the types of (noninvasive) fetal screening (four)?
- Ultrasound
- Fetal MRI
- Maternal Serum Screening
- Sequencing of cffDNA
What are the types of diagnostic (invasive) prenatal testing (five)?
- Chorionic villus sampling (CVS)
- Amniocentesis
- Cordocentesis
- Fetal Biopsy
- Pre-implantation genetic diagnosis (PGD)
The dating ultrasound is performed at what time during pregnancy?
First trimester, 8-10 weeks.
NIPT begins at what what week in pregnancy?
First trimester, 9-10 weeks (and later).
The first maternal serum screening occurs at what time in pregnancy?
First trimester, 11-13 weeks, the same time as NT.
NT
Nuchal translucency.
Nuchal translucency is measured at what time during pregnancy?
First trimester, 11-13 weeks, the same time as MSS.
CVS is performed at what time during pregnancy?
First trimester, 11-13 weeks.
What tests are performed during the first trimester (three)?
- Dating ultrasound
- Nuchal Translucency
- Serum Screening
- CVS
The second maternal serum screening occurs at what time during pregnancy?
Second trimester, 15-18 weeks.
Amniocentesis is performed at what time during pregnancy?
Second trimester, 15-19 weeks.
Fetal anomaly scan is performed at what time during pregnancy?
Second trimester, 18-20 weeks.
What are the advantages to ultrasonography (four)?
- No harm to fetus or mother.
- Performed at any gestational age.
- Allows two and three-dimensional imaging.
- Real time imaging of fetal movement.
What are some disadvantages to ultrasonography (two)?
- Not 100% diagnostic
- Fetal heart anomalies are very difficult to diagnose.
Indications for invasive diagnosis (six):
- Maternal age 35 or older at time of delivery.
- Major structural anomaly on US.
- Abnormal serum screen.
- Positive cfDNA result.
- Family hx of single gene disorder or chromosome abnormality.
- Maternal anxiety.
What is nuchal translucency and what is it used for?
It is a measurement of the fluid-filled space between the back of the fetal neck and overlying skin.
Increased in fetuses with:
- Trisomies 13, 18, and 21
- Turner Syndrome (45,X)
- Triploidy (69 chromosomes)
What is maternal serum screening?
Measurement of proteins produced by fetus or placenta.
-Is usually calculated relative to population standards (MoM)
What must be known in order to evaluated a maternal serum screen (five)?
- Gestational age
- Maternal Age
- Maternal Race
- Presence of Diabetes
- Smoking status
The first maternal serum screen measures (two):
- PAPP-A
2. β-hCG
PAPP-A
Pregnancy-associated plasma protein A
The second maternal serum screen measures (four):
- AFP
- β-hCG
- uE3
- Inhibin
What kind of PAPP-A and free β-hCG levels would be expected in a fetus with down syndrome?
- Low PAPP-A
- High free β-hCG
What is the next step if a fetus has a positive MSS for down syndrome?
Offer of invasive procedure.
CVS
Chorionic Villus Sampling
What is CVS?
An invasive procedure that involves transabdominal aspiration of a small amount of tissue from the placenta.
What are the benefits of CVS (four)?
- Restores privacy to reproductive decisions (before mother is showing).
- Mitotically active cells allow for rapid karyotyping.
- Tissue obtained is preferable for DNA analysis.
- Will detect fetuses at risk for UPD.
What are the risks/disadvantages of CVS (five)?
- Elevated risk of fetal loss (0.5-1.0%)
- Slight risk of maternal infection.
- Possible limb malformation.
- Confined placental mosaicism.
- Amniotic fluid alpha fetoprotein not assayed (no neural tube defect information).
What is amniocentesis?
It is an invasive procedure that involves transabdominal aspiration of amniotic fluid that surrounds the fetus.
Where do the cells acquired from amniocentesis come originate?
The fetal mouth, bladder, and amnios.
What is a risk of amniocentesis and how can it be reduced?
Fetal club foot can occur if performed from 11-13 weeks. Risks can be reduced by performing at 15-17 weeks.
FISH analysis of non-dividing cells from amniocentesis can rapidly diagnose what?
Aneuploidy.
Where does one find cell-free fetal DNA (cffDNA)?
Maternal blood.
Where does cffDNA originate?
The placenta.
cffDNA sequencing can provide information about (three)…
- Fetal sex.
- Trisomies 13, 18, and 21.
- Sex chromosome abnormalities.
What are the limitations of NIPT (three)?
- Finite amount of cffDNA (especially difficult in overweight mothers).
- Less reliable with twins.
- Will not detect open neural tube defects.
What is PGD?
Pre-implantation genetic diagnosis.
It is the process of screening embryos for genetic abnormalities before transferring to the uterus.
Note: This requires IVF.
Where is the material for PGD acquired and what tests are run on it (two)?
A single cell from a blastomere.
FISH and PCR.
True or false?
PGD has approximately the same pregnancy rate as natural conception efforts.
True.
True or False?
PGD has increased risks for birth defects.
False.
There are no increased risks for birth defects with PGD.
What are the widely accepted clinical applications of PGD with subsequent PCR analysis, FISH, or sex selection (six, two each)?
- Autosomal conditions (PCR)
- Untreatable or lethal X-linked conditions (PCR)
- Reciprocal or Robertsonian translocation (FISH)
- Pericentric inversion (FISH)
- Autism (sex selection)
- X-linked conditions (sex selection)
What are four controversial indications for PGD (four)?
- Pre-disposition for adult-onset disorders (insurance)
i. e. breast cancer, autosomal dominant cancer syndromes - Aneuploidy screening by FISH for AMA, recurrent SAB, repeated IVF failure.
- Sex selection for “family balance.”
- Creation of HLA-matched stem cell donors (savior children).
What does the future hold for prenatal genetics?
Whole genome sequencing of fDNA and prenatal treatment of genetic disorders.
