MCP 10 Flashcards
Indications for prenatal diagnosis
- Familial chromosome anomaly
- family history of a genetic disorder for which testing is available
- familial x linked recessive disorders without testing available
- increased risk of ONTD
- carrier of genetic disorder
- consanguinity (identity by descent)
Define prenatal diagnosis
Medical evaluation of the fetus that provides both physical and genetic information
Genetic testing has the capability to diagnose fetal disease
Prior to testing parents should be counseled about reasons to do the test and possible outcomes
Depending on the type of test there could be a risk to the mom and the pregnancy
Other indications for prenatal diagnosis
- ultrasounds anomaly
- repeated miscarriage
- abnormal MSAFP
- anxiety
- environmental exposures
- increased risk of chromosomal abnormality
Invasive versus non invasive
In general noninvasive is better than non invasive is less risky
Want the most specific result with lowest risk
Type of testing performed depends on clinical indication and what information needs to be collected
Ultrasound
Verify viability Defect a multiple pregnancy Determine gestational age Identify possible abnormalities May indicate that additional studies are warranted
What does the ultrasound anomaly of nuchal translucency ?
One indicator of possible fetal abnormality thickness of 6 mm has been associated with downs
Maternal serum alfaprotein
AFP is an albumin type protein made by the fetal liver and crosses the placenta allowing it to be detected in maternal circulation
- rises and falls with gestation, highest around 15-20 weeks
- test is sensitive to a number of variables including the mothers weight, race and diabetic status
- about 1-2% of the initial screen will be elevated, of these only 1/15 will show an anomaly upon further testing
MSAFP, screening test ranges and associated risks
low -levels-> indicative of possible Down syndrome and other chromosome anomalies
high levels- ONTD
List the components of a Maternal serum quad test and what values would indicate a finding of Down’s syndrome
- alpha fetoprotein (AFP) - decreased
- human chorionic gonadotropin (HCG) - elevated
- unconjugated estriol (uE3)- decreased
- dimeric inhibin-A (gylcoprotein hormone secreted by the ovary) -increased
- -80% combined detection rate for downs
Non-invasive prenatal screening test
- a sample of the mothers DNA is taking at 10-22 weeks gestation, cfDNA cell free dna is isolated. This will be comprised of DNA from both the mother and fetus and only about 10-15% is fetal, most of the fetal DNA is actually derived from the placenta and other extraembyronic tissues
-> test including: sequencing of the DNA fragments, determine chromosomal source of each fragment and statistically analyze the
number of fragments per chromosome compared to expected number for mother and fetus - specialized software is used to evalute possible aneuploidy
Amniocentesis
-a procedure where a needle is inserted through the abdomen into the amniotic cavity -and amniotic fluid is withdrawn for testing (invasive procedure) done with ultrasound guidance and is performed at 16-18 months gestation, but early amniocentesis can be done at the 13 to 14 mark.
-risk is fetal loss in 1/200
tests performed on the specimen obtained include: cytogenetics, metabolic assays and molecular diagnostics and AFAFP
What diseases/conditions are low AFP levels associated with
- trisomies 13,18 and 21
- mosaic Turner syndrome
- triploidy
- unbalanced translocations
What disease/conditions are associated with elevated levels of AFP?
- open NTD
- closed neural tube defects (less so)
- multiple pregnancies
- fetal death
- body wall defect
- anencephaly
- small mother
- monozygotic twin pregnancy
What is the confirmatory test for NTD?
-acetylcholinesterase is the confirmatory test -> aChE should only be present in amniotic fluid if there is a defect in the neural tube –> the only source of ACH in a normal person is the neural tube so if it is found in high concentrations then it must have escaped via some type of body opening
Chorionic villus sampling (CVS)
-samples the placenta instead of fetal tissues -works because the placenta is derived from the original zygote
-performed at 10-14 weeks gestation
-there is a risk of limb reduction if the procedure is done before the 10 week mark -> because it may remove cells necessary for circulation and if done limbs can fail to grow
studies that can be done on collected specimens include: cytogenetics, metabolic assay and molecular genetics (cannot do AFP because no fluid is collected)
-risk slightly higher than in amniocentesis 1/100 fetal loss risk
