Genetics in Medicine: Prenatal Screening and Diagnosis

Flashcards about prenatal screening and diagnosis, covering topics such as screening for neural tube defects and aneuploidies, noninvasive prenatal screening, prenatal diagnosis methods, and genetic testing.

*What is prenatal screening?

Testing in pregnancies not known to be at risk for certain common birth defects like chromosomal aneuploidies, neural tube defects, and other structural anomalies.

What is a major advancement in noninvasive prenatal screening?

Sequencing of cell-free DNA in maternal blood.

*What is the goal of prenatal screening?

To identify pregnancies that should be offered prenatal diagnostic testing.

What is MSAFP often assayed in conjunction with to screen for neural tube defects?

Ultrasound (US).

What analytes and measurements are evaluated during first-trimester screening for aneuploidies?

Pregnancy-associated protein A (PAPP-A) - decreased in trisomies

human chorionic gonadotropin (HCG) - elevated in trisomy 21, depressed in other trisomies

Nuchal translucency (NT) via ultrasound - increased in trisomies and monosomy 45,X

*What analytes are measured in the quadruple screen during the second trimester screening for aneuploidies?

When does a pregnant woman's serum contain fetal DNA that is floating freely?

After 7 weeks of gestation - related to NIPS

What technological discovery made Noninvasive Prenatal Screening (NIPS) possible?

High-throughput sequencing methods.

Is Noninvasive Prenatal Screening (NIPS) a screening test or diagnostic test?

A screening test, not diagnostic.

What is prenatal diagnosis?

Testing a fetus already known to be at elevated risk for a condition.

• birth of previous child with disease

• family hx of disorder

• positive parental carrier test

• positive prenatal screening test

*usually uses chorionic villus sampling for amniocentesis

What type of test is typically required for prenatal diagnosis?

Chorionic villus sampling (CVS) or amniocentesis.

What are some indications for prenatal diagnosis by invasive testing?

Previous child with genomic imbalance, structural chromosome or genome abnormality in a parent, family history of genetic disorder, increased risk based on screening tests.

What is amniocentesis?

Inserting a needle transabdominally into the amniotic sac to obtain a sample of amniotic fluid.

When is amniocentesis typically performed?

Between weeks 16 and 20 of gestation.

What is chorionic villus sampling (CVS)?

Biopsy of the tissue from the villi of the chorion, transcervically or transabdominally.

When is chorionic villus sampling (CVS) typically performed?

Between weeks 10 and 13 of gestation.

What is preimplantation genetic diagnosis (PGD)?

Testing during IVF to select embryos free of a specific genetic condition before transfer to the uterus.

How is diagnosis made for preimplantation genetic diagnosis(PGD)?

PCR, FISH, or chromosomal microarray (CMA).

What is a blastomere biopsy?

A single cell is removed 3 days after IVF at the 8-16 cell stage.

What is a blastocyst biopsy?

~5 cells are removed from the trophectoderm 5-6 days after IVF.

What test can be used to rapidly test for aneuploidy when needed?

FISH (fluorescent in situ hybridization).

What test should be the 1st-line test when a fetal abnormality is found on ultrasound?

Chromosome microarray analysis.

What can be a problem with CVS samples?

CVS samples the extra-embryonic tissues of the placenta, not the fetus itself.

At the level of public health, what has led to a major decline in incidence of a few serious disorders, such as beta-thalassemia and Tay-Sachs?

Prenatal diagnosis combined with elective termination.

What are typical prenatal screenings able to detect?

• chromosomal aneuploidies

• neural birth defects

• other structural anomalies

Tends to be non-invasive such as blood sampling

*What is the advantage of using cell-free DNA testing over other forms of prenatal screening

What are AFP levels used to detect? *What is the difference between AFAFP and MSAFP?

• Alphafetoprotein (AFP) is used to measure amniotic fluid and maternal serum (MSAFP) and can be obtained in a noninvasive manner at 16 weeks

  • if AFP levels are elevated then may need to look for neural tube defect

  • MSAFP is screened with ultrasound

describe the three first trimester procedures used to test for aneuploidies

• Evaluation of analytes along with ultrasound between 11-13 weeks

• Pregnancy associated protein (PAPP-A) - decreased trisomies

• Human Chorionic Gonadotropin (HCG) - elevated in trisomy 21, depressed in other trisomies

• U/S used to measure nuchal translucency (NL) - increased in trisomies and monosomy 45,X

describe the four second trimester procedures used to test for aneuploidies

Second trimester screening is a quadruple screen:

• HCG - elevated in trisomy 21, depressed in other trisomies

• Maternal serum AFP - depressed

• Unconjugated estriol - depressed

• Inhibin A - elevated in trisomy 21, unaffected in other trisomies

Describe what is meant by NIPS and give an example

• NIPS is

What factors of a pregnancy indicate “elevated risk”?

Describe Ultrasound and how it is useful in prenatal screening

Describe amniocentesis and the pros and cons of using it in prenatal screening

. Describe chorionic villus sampling and the pros and cons of using it in prenatal screening

describe PIGD

Describe a few problems associated with assessing prenatal screening results