Lecture 10: Prenatal Genetics Flashcards
Indications for Prenatal Dx - Inherited
Familial chromosome
anomaly, Family history of a genetic disorder for
which testing is available, Familial X linked recessive disorder without testing available, Increased risk of ONTD (recurrence risk 2-5%), Carrier of genetic disorder, ethnic risk, Consanguinity –Identity by descent.
Indications for PND - Other
Ultrasound anomaly, Repeated miscarriages, Abnormal MSAFP, Anxiety, Env exposures, Increased risk for chromosomal abnormality (older moms).
What 3 things are non-invasive tests? What 3 are invasive?
Examination, ultrasound, MSAFP. Cytogenetics, biochemical, and molecular studies.
What type of anomalies are detectable by ultrasound?
Nuchal translucency, clefting, NTDs.
Explain MSAFP
Non-invasive blood test done at 15-20 wks. AFP is produced by fetal liver and crosses the placenta into maternal circ. The value obtained in maternal circ is compared to statistical standards. The level is correlated with stage of gestation. It’s sensitive to mother’s weight, race, and diabetic status. About 1-2% of the time the inital screen will be elevated, but of these only about 1 in 15 show an anomaly with further screening.
MSAFP is a screening test for risk assessment, meaning they give the possibilities of the outcome of the pregnancy. Low levels may mean what? High levels?
DS, ONTD.
The Maternal Serum Quad Test (@15-21 wks) looks at 4 different preg related hormones. In testing for the risk of DS, what are the parameters?
Low AFP, high hCG, low uE3, low dimeric inhibin A.
“Integrated” Prenatal Testing is performed betw 10-13 wks gestation and combines morphologic data with biochemical analysis. What are the parameters looked at here?
PAPP-A (when low, inc’d risk of DS), nuchal translucency.
What is the newest non-invasive assay known as? What is it measuring?
NIPT - cfDNA isolated from maternal blood at 10-22 wks, 10-15% of the total being fetal in origin.
In NIPT, NGS is used to detm how much of the cfDNA is fetal, and specialized software is used to analyze the expected amounts of DNA per chromosome to see if there’s an inc or dec in the total value for a particular chrom that would suggest an aneuploidy. If a number is out of bounds, what happens next?
It has to be confirmed by a diagnostic test which is usually karyo anal &/or FISH performed on amniotic fluid collected by amniocentesis.
What studies can be performed on either fetal cells or fluid gathered from amniocentesis?
AFAFP, cytogenetics, metabolic assays, molecular diagnostics
Low AFP levels are assoc’d with a variety of different chrom abn’s. Name some. What tests then confirm it?
Trisomies 13,18,21; Mosaic Turner syndrome; Triploidy, unbalanced translocations. Karyotype analysis.
Elevated AFP levels are assoc’d with? What tests confirms it?
Inc’d risk ONTD or body wall defect. AChE test (ACh should only be present in amniotic fluid if there’s a defect in the neural tube.
CVS carries a risk of what by removing cells necessary for the developing circulation in the extremities when performed before 10 weeks gestation?
Limb reduction
Since no fluid is collected during CVS, what’s the downside? What can it test? What does it actually sample? What is done if the CVS test is abnormal?
AFP can’t be tested. Tests cytogenetics, molec diagnostics, and metabolic (cells only). CVS samples the placenta instead of fetal tissues (usu biologically the same). Amniocentesis.
