Prenatal Genetics

Question 1

What is genetic testing capable of doing? Prior to testing, what should be done with the parents?

Answer 1

Diagnosing fetal disease; should be counseled about why we’re doing the test and the possible outcomes

Question 2

What is an indication for prenatal diagnosis (inherited)?

Answer 2

Familial chromosome anomaly (structural chromosome rearrangement; chromosome abnormality); family history of a genetic disorder (with testing AVAILABLE); familial X linked recessive disorder with NO TESTING; increased risk of open neural tube defects (multifactorial); carrier of genetic disorder and ethnic risk (e.g. CF and Jews); consanguinity (ID by descent)

Question 3

What are indications for prenatal diagnosis (other)?

Answer 3

US anomaly; repeated miscarriages; abnormal MSAFP (maternal serum alphafetoprotein) with high and low levels; environmental exposures (smoking, rec drug use, exposures at work, infections); risk of chromosomal abnormality

Question 4

To whom do chromosomal abnormalities occur? What is the most common live born chromosome anomaly? What is the most common aneuploidy? What is the most common autosomal aneuploidy?

Answer 4

Older moms typically; trisomy 21; 45,X; trisomy 16

Question 5

When do most spontaneous termination frequencies occur?

Answer 5

95% of 45,X conceptions

Question 6

What are non-invasive tests? What are invasive tests?

Answer 6

Examination and ultrasound; cytogenetics, biochemical, and molecular studies

Question 7

In general what is better, non-invasive vs. invasive?

Answer 7

Non-invasive (less risk to fetus);

Question 8

What can ultrasound help you do? What is an anomaly with US? What else can US find?

Answer 8

1. verify viability 2. detect multiple pregnancies 3. determine gestational age 4. determine sex 5. identify possible abnormalities; nuchal translucency (possible chromosomal anomaly); clefting (multifactorial); neural tube defects (meningomyelocele that could be open or closed)

Question 9

What are two examples of neural tube defects? Can it be repaired?

Answer 9

Anencephaly (absence of brain and lethal) and encephalocele (brain extruded from the skull); rarely

Question 10

What type of test is maternal serum alphafetoprotein? What signals a potential problem? When is MSAFP most often sampled? What variables do you have to consider?

Answer 10

Non-invasive blood test; too high or low of MSAFP; 15-20 weeks (usually 16-18 weeks); consider mother’s weight (higher levels in larger woman), race, and diabetic status

Question 11

What does a level of MSAFP of 1 indicate? Can it be used for diagnosis?

Answer 11

Could be a normal unaffected individual or a fetus with Down syndrome; No, just risk assessment (not diagnostic)

Question 12

What does maternal serum quad test? What can it help detect specifically? Compared to MSAFP testing, who can quad test be used on?

Answer 12

alpha-fetoprotein (low); hCG (high); unconugated estriol (low); dimeric inhibin-A (high); Down Syndrome; Up to 40 years of age (only 35 for MASFP)

Question 13

What does integrated prenatal testing include? When cn you start it?

Answer 13

10-13 weeks gestation; PAPP-A (pregnancy-associated plasma protein-A if down increases risk of DS) along with nuchal translucency

Question 14

What is the newest non-invasive assay? When do you take mother’s blood? What is isolated? How much of the DNA is going to be isolated belonging to the fetus?

Answer 14

NIPT or NIPS (non-invasive prenatal screening); 10-22 weeks; cell free fetal/placental DNA (mother and fetal DNA); 10-15% of total being fetal in origin

Question 15

Is NIPT/NIPS a diagnostic study? What can be a follow-up test to this?

Answer 15

NOOOOOO; screening test that gives risk for chromosomal abnormality; use karyotype analysis and/or FISH performed on amniotic fluid collected by amniocentesis

Question 16

How accurate is NIPS for DS and trisomy? What can lead to the test failing? Fail rate for NIPS?

Answer 16

99% with few false positives; insufficient fetal DNA;

.5-7%

Question 17

What are two invasive procedures?

Answer 17

Amniocentesis and chorionic villus sampling

Question 18

How is amniocentesis conducted? What is withdrawn? When can it be performed? What are the tests possible given amniocentesis?

Answer 18

Transabdominally; amniotic fluid; usually performed 16-18 weeks (can start at 13-14 weeks); AFAFP, cytogenetics, metabolic assays, molecular diagnostics

Question 19

Is AFAFP considered a diagnostic test? Given AFAFP, what are low levels associated with?

Answer 19

Still a screening test; Trisomies 13, 18, 21, mosaic Turner syndrome, triploidy, unbalance translocations

Question 20

What levels are elevated with MSAFP vs. AFAFP? When are the levels the same?

Answer 20

Multiple pregnancy and small mothers; ONTD and anencephaly

Question 21

If AFAFP is high, is this a diagnostic test? What can be used to confirm? Where would AchE only ever be present for a path? What can low AFP be associated with? What can confirm this risk assessment?

Answer 21

No, just a screening test; use acetylcholinesterase for a confirmatory test; only if there is a defect in the neural tube; Chromosomal disorders like Down syndrome; karyotype

Question 22

When does CVS occur? What is a potential consequence of doing it too early? What does CVS usually sample? What are the tests involved?

Answer 22

10-14 weeks gestation; limb reduction <10 weeks; Placenta instead of fetal tissues; Cytogenetics, molecular diagnostics, metabolic (cells only)

Question 23

What does CVS rely on with respect to placental and fetal cells? Does this then allow for mosaicism? What is a false positive in this case, false negative?

Answer 23

Them being the same; yes, just you need mosaicism to occur among both cell types; localized mutation (placental) but fetal cells unaffected; confined mutation (fetal cells with placental cells unaffected)

Question 24

Why would you choose CVS? What risks might want someone to consider early termination?

Answer 24

Couple wants to know early on if there’s a problem so they could have pregnancy terminated; consider CF, DMD, translocation/inversion carrier, aneuploidy

Question 25

What are outcomes of prenatal diagnosis?

Answer 25

No anomalies in 98% of cases; termination, fetal treatment in utero (fetal open heart surgery, urinary tract repairs), IVF

Question 26

What are two examples of assisted reproductive technologies? What can polar body analysis help with?

Answer 26

IVF and donor eggs; Check the first polar body to see if mutation (e.g. CF) is present

Question 27

What does PGD help do?

Answer 27

Screening technique for embryos; at 8 cell stage, single cell is separated out and tested either by FISH or molecular assay, depending on info needed; CANNOT USE karyotypes (no metaphase cells)

Question 28

What is beginning to replace PGD?

Answer 28

Next generation sequencing because it’s a whole genome screen