Prenatal Genetics Flashcards
What is genetic testing capable of doing? Prior to testing, what should be done with the parents?
Diagnosing fetal disease; should be counseled about why we’re doing the test and the possible outcomes
What is an indication for prenatal diagnosis (inherited)?
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)
What are indications for prenatal diagnosis (other)?
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
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?
Older moms typically; trisomy 21; 45,X; trisomy 16
When do most spontaneous termination frequencies occur?
95% of 45,X conceptions
What are non-invasive tests? What are invasive tests?
Examination and ultrasound; cytogenetics, biochemical, and molecular studies
In general what is better, non-invasive vs. invasive?
Non-invasive (less risk to fetus);
What can ultrasound help you do? What is an anomaly with US? What else can US find?
- 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)
What are two examples of neural tube defects? Can it be repaired?
Anencephaly (absence of brain and lethal) and encephalocele (brain extruded from the skull); rarely
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?
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
What does a level of MSAFP of 1 indicate? Can it be used for diagnosis?
Could be a normal unaffected individual or a fetus with Down syndrome; No, just risk assessment (not diagnostic)
What does maternal serum quad test? What can it help detect specifically? Compared to MSAFP testing, who can quad test be used on?
alpha-fetoprotein (low); hCG (high); unconugated estriol (low); dimeric inhibin-A (high); Down Syndrome; Up to 40 years of age (only 35 for MASFP)
What does integrated prenatal testing include? When cn you start it?
10-13 weeks gestation; PAPP-A (pregnancy-associated plasma protein-A if down increases risk of DS) along with nuchal translucency
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?
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
Is NIPT/NIPS a diagnostic study? What can be a follow-up test to this?
NOOOOOO; screening test that gives risk for chromosomal abnormality; use karyotype analysis and/or FISH performed on amniotic fluid collected by amniocentesis
How accurate is NIPS for DS and trisomy? What can lead to the test failing? Fail rate for NIPS?
99% with few false positives; insufficient fetal DNA;
.5-7%
What are two invasive procedures?
Amniocentesis and chorionic villus sampling
How is amniocentesis conducted? What is withdrawn? When can it be performed? What are the tests possible given amniocentesis?
Transabdominally; amniotic fluid; usually performed 16-18 weeks (can start at 13-14 weeks); AFAFP, cytogenetics, metabolic assays, molecular diagnostics
Is AFAFP considered a diagnostic test? Given AFAFP, what are low levels associated with?
Still a screening test; Trisomies 13, 18, 21, mosaic Turner syndrome, triploidy, unbalance translocations
What levels are elevated with MSAFP vs. AFAFP? When are the levels the same?
Multiple pregnancy and small mothers; ONTD and anencephaly
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?
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
When does CVS occur? What is a potential consequence of doing it too early? What does CVS usually sample? What are the tests involved?
10-14 weeks gestation; limb reduction <10 weeks; Placenta instead of fetal tissues; Cytogenetics, molecular diagnostics, metabolic (cells only)
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?
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)
Why would you choose CVS? What risks might want someone to consider early termination?
Couple wants to know early on if there’s a problem so they could have pregnancy terminated; consider CF, DMD, translocation/inversion carrier, aneuploidy
What are outcomes of prenatal diagnosis?
No anomalies in 98% of cases; termination, fetal treatment in utero (fetal open heart surgery, urinary tract repairs), IVF
What are two examples of assisted reproductive technologies? What can polar body analysis help with?
IVF and donor eggs; Check the first polar body to see if mutation (e.g. CF) is present
What does PGD help do?
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)
What is beginning to replace PGD?
Next generation sequencing because it’s a whole genome screen
