Lecture 9: Prenatal Genetics Flashcards
Is the recurrence risk for open neural tube defect high or low? why?
high
multifactorial; gene + env
What is MSAFP dnd what is an abnormality an indication for?
maternal serum alphafetoprotein
high/low –> fetal abnormalities
prenatal diagnosis
What are the most common aneuploidy and autosomal aneupolidy in spontaneous abortion?
45,X (95% will terminate spontaneously)
Trisomy 16
What are the non-invasive tests for prenatal genetics?
examination
ultrasound
Testing Maternal AFP
What are the invasive tests for prenatal genetics?
cytogenics biochemical molecular studies Testing fetal AFP Amniocentesis CVS
Why are some prenatal tests considered invasive?
needle inserted to collect fetal cells, tissues, or fluids
What does nuchal translucency on an ultrasound indicate?
possible xs abormality
What fetal anomalies can ultrasounds detect?
nuchal translucency, clefting, neural tube defects (NTD)
Where is AFP produced, and what is the test sensitive to?
produced in fetal liver, found in mother’s serum
test is sensitive to mother’s WEIGHT, race, diabetic status
What do high/low level of AFP indicate?
Low = down syndrome; xs anomaly High = NTD
is AFP used for diagnosis?
No - risk assessment
What method is used to detect Down Syndrome?
Maternal Serum Quad Test
If a lab cannot determine nuchal translucency as a screen for Down Syndrome, what tests can they offer?
PAPP-A + Maternal Serum Quad Test
what is NIPS(/NIPT)?
Non-Invasive Prenatal Screening(/Testing)
How and when is NIPS performed?
use cfpDNA (cell free placental) at 10-22 weeks
then sequence
use precise software to analyze aneuploidies present
After NIPS, how would diagnosis be performed?
Karyotype analysis
FISH on amniotic fluid
Which is more accurate: NIPS or serum screening?
NIPS
What is amniocentesis? When is it performed?
Needle goes into amniotic cavity, draws amniotic fluid
16-18 weeks
early: 13/14 weeks
Which is more risky - early or later amniocentesis? Why?
early is riskier
not as much amniotic fluid - could remove too much –> loss of mobility of fetus –> developmental defects
What tests can be performed after amniocentesis?
AFAFP (like MFAFP)
Cytogenetics
Metabolic Assays
Molecular diagnostics
what must be know for AFAFP/MFAFP testing?
gestational age
known standards for comparison
What are low AFP levels indicative of?
Trisomies 13, 18, 21
Mosaic Turner Syndrome
Tiploidy
Unbalanced translocations
What are high levels of AFP indicative of?
teratoma renal obstruction/agenesis uropathy upper GI obstruction bladder/cloacal exstrophy
What are reasonable explanations for increased AFP levels??
gestational age incorrectly reported
mom’s weigh nigh/low
twins
How is high AFAFP confirmed?
Ach test
Ach is only found in neural tube
If it is found in amniotic fluid, it must have escaped through a defect
How is low AFAFP confirmed?
Karyotype analysis
What is a risk of CVS?
limb reduction
What studies cannot be performed with CVS?
AFP studies - no fluid collected
What studies are performed with CVS?
cytogenics
metabolic assays on cells
molecular diagnostics
What does CVS test? What does it not test?
Placenta
NOT fetal tissue
How must abnormal CVS results be confirmed?
amniocentesis
What type of mosaicism gives the most accurate CVS findings?
Complete - found in both fetus and placenta
Why can CVS be advantageous?
can be performed in first trimester - can abort sooner
what is non-directive genetic counseling?
family decides
What is intracytoplasmic sperm insertion (ICSI) and when is it used?
single sperm injected into egg
low sperm count
What is in vitro fertilization? How does implantation then occur?
fertilization in petri dish
embryos are tested
appropriate ones undergo zygote intrafallopian transfer (ZIFT)
When is polar body analysis useful?
determining which IVF embryo to implant
both parents are carriers
if polar body has mutation, oocyte doesn’t
What is Preimplantation Genetic Diagnosis?
8-cell stage: one cell tested by FISH
interpret xs composition
Why can’t karyotype analysis not an option with Preimplantation Genetic Diagnosis?
no metaphase cell
What type of egg donor technology can be used for a woman who has a mitochondrial defect?
swap nucleii
have most of bio mom’s genes; don’t have mito defect
