Prenatal Genetics

Question 0

Maternal serum alphafetoprotein

Answer 0

MSAFP is a noninvasive blood test
AFP is an albumin like protein produced by fetal liver
Crosses the placenta, can be detected in mother’s blood
Level of AFP correlated to stage of gestation because it rises and falls during development
Sampled 16-18 weeks, problem if too high (open spina bifida) or low (Down syndrome)
Sensitive to mother’s weight, race, diabetes status

Question 1

Ultrasound

Answer 1

~18 weeks, noninvasive
Detect variety of defects, verify viability, multiple pregnancy, gestational age, sex

Detectable Anomalies:

Nuchal translucency-clear space in tissue at back of baby’s neck means Down syndrome if thick enough
Clefting
Neural tube defects-anencephaly is absence of brain and encephalocele is when brain extrudes from skull

Question 2

Maternal serum quad test

Answer 2

4 substances for higher sensitivity than AFP testing alone

AFP low, hCG high, unconjugated estriol low, dimeric inhibin A high
=Down syndrome

Question 3

Integrated prenatal testing

Answer 3

Combines morphologic data with biochemical analysis

10-13 weeks: risk of Down syndrome if low PAPP-A (pregnancy-associated plasma protein A); nuchal translucency
15-21 weeks: quad MSAFP test performed

Question 4

Non-invasive prenatal screening (NIPS)

Answer 4

Sample taken of cell-free DNA (cfDNA) which contain free floating DNA from both mother and the placenta/fetus
CfDNA chromosome origin identified with DNA sequencing
Compare results with expected frequency of fragments from each chromosome for both pregnant and non-pregnant women
Any increase or decrease suggests an aneuploidy

Question 5

Amniocentesis

Answer 5

Invasive procedure where a needle is inserted through abdomen into amniotic cavity to get amniotic fluid for study on amniotic fluid AFP (AFAFP) which should confirm MSAFP results

Low level of AFP: trisomies, mosaic Turner syndrome, triploidy, unbalanced translocations; confirm with karyotype analysis/FISH

High level of AFP: ONTD (open neural tube defects); confirm with acetylcholinesterase test

Question 6

Chorionic villus sampling (CVS)

Answer 6

Samples placenta transabdominally or transvaginally (placenta and fetus are derived from original zygote so are biologically the same), then can do cytogenetics, metabolic assay, molecular diagnostics on cells (for known mutations, CF, DMD, translocation or inversion, older mom)

Risk of limb reduction if done prior to 10 weeks gestation

No fluid collected so no AFP studies, use amniocentesis to confirm abnormal results instead

Complete mosaicism if mutations occur in fetal and placental cells
Localized mutation (placenta) if only in placenta cells->false positive 
Confined fetal mutation if only in fetal cells->false negative

Question 7

Outcomes of prenatal diagnosis

Answer 7

Termination, fetal treatment in utero, in vitro fertilization

Question 8

Polar body analysis

Answer 8

Assisted reproductive technology where it is known that one or both partners carry a gene mutation
Test first polar body for mutation, if yes, then secondary oocyte is okay, if no then oocyte is eliminated

This is before fertilization

Question 9

Preimplantation genetic diagnosis (PGD)

Answer 9

ART where general assays like FISH is used to look for chromosome aneuploidies then unsatisfactory embryos are destroyed

This is after fertilization