MCM 2-38 Prenatal Genetics Flashcards
goal of prenatal genetics?
help mothers/families make decisions about pregnancies based on family medical history, knowledge of relevant disorders, possible outcomes, and options available to them.
families may need information both before and after testing, and it must be
supportive, confidential, and non-directive (family must decide for themselves)
indications for prenatal diagnosis include
familial chromosome anomaly
family history of genetic disorder with testing available
familial x-linked recessive disorders for which testing is not available
increased risks of ONTD’s
carrier or ethnic risk of genetic disorder
ultrasound anomoly
repeated miscarriages
ONTD’s
open neural tube defects including spina bifida
ultrasound show be used when during pregnancy?
throughout pregnancy to get information about embryo and to follow devlopment/catch any abnormalities
Alpha-Fetoprotein Testing (AFP testing)
produced where?
when does it peak?
what effects the expected level?
low levels suggest?
high levels?
non invasive screening, detects alpha-fetoprotein
AFP produced in unborn child that crosses placenta
AFP in mother is referred to as maternal serum AFP (MSAFP)
levels peak at 15-20 weeks
weight/race/diabetic status will effect expected level
low levels - suggest downs or other chromosome anamolies
high levels - neural tube defects (ONTD’s)
describe quad screening
detects what?
when used?
expansion upon AFP testing used to detect four substances
AFP, hCG, unconjugated estradiole (uE3), Dimeric inhibin A
substance amounts are associated with different gestational ages. between weeks 15-21. not a diagnostic, a risk estimate
hCG and downs?
increased levels suggest downs
unconjugated estradiol (uE3) and downs?
decreased levels suggest downs
dimeric inhibin A levels and downs?
increased levels, suggest downs
integrated testing
when?
between weeks 10 and 13
nuchal translucency (ultrasound test) and pregnancy associated plasma protein A (decreased levels suggest downs)
pregnancy associated plasma protein A levels and downs?
decreased levels suggest downs
Non-Invasive prenatal screening (NIPS)
how is it done?
what are the limitations?
give risk estmate, used to screen for trisomy 13, 18, 21 and X and Y abnormalities
based off of NGS testing for cell-free placental DNA in maternal blood between 10-22 weeks
- genome sequencing identifiies DNA fragments and then chromosomal source of each fragment determined
- statistical analysis (counting) compares numbers.
- cant discern mother abnormalities from fetal
- cant discern dna from vanished twin
- cant discern tripoloidy (all chromosome levels will be equal, unlike downs which would have 50% more chromosome 21 than other chromsoomes)
amniocentesis
when used?
risk?
subsequent tests?
invasive technique that draws cells from amniotic fluid from amniotic cavity
between weeks 16 and 18
carries termination risk for fetus
Amniotic fluid AFP
cytogenetics (fish and karyotype analysis to confirm downs)
metabolic assays
molecular diagnositcs (acetylcholinaterinase to confirm ONTDs)
Chorionic Villi Sampling
risk?
advantage?
invasive technique that samples cells from placenta, performed between weeks 10-14 but no earlier as can cause limb reduction.
higher termination risk than amniocentesis
any abnormalities found must be confirmed
advantage - performed earlier than amnio, earlier termination is easier physically and pscyhologically.
Your 38 year old patient miscarries at 15 weeks gestation. Cytogenetic analysis reveals that the fetus has trisomy 13 (47,XY,+13). Which of the following is the correct next step?
A. Karyotype both parents to determine the recurrence risk.
B. Karyotype the mother only since this is the most likely source of the abnormality.
C. Perform molecular testing to confirm the diagnosis.
D. Counsel the family on the nature of trisomy 13 and provide a recurrence risk.
E. Both A and D should be done.
D. Counsel the family on the nature of trisomy 13 and provide a recurrence risk.
Trisomy 13 is a sporadic nondisjunction error, so neither parent will have a chromosomal abnormality that would aid in counseling. Parental karyotypes would be useful if a translocation had been founD. D. If the cytogenetic test is positive, it does not need to be confirmed by addtional testing. The cytogenetic results are all that is needed for counseling and risk assessment.
Ann is 25 years old and is 20 weeks pregnant. She has a family history of cystic fibrosis (CF), and is concerned about having a child affected with the disorder. Which of the following is the most appropriate first step to take in handling this case?
A. Perform amniocentesis and assay the fetal cells for the presence of disease causing genes.
B. Test both parents and determine if a CF mutation can be identified in either individual.
C. Explain to Ann this is a manageable disease and advise her to wait until the baby is born before testing so that there is no risk to the pregnancy.
D. Perform MSAFP testing to assess the risk to the fetus.
B. Test both parents and determine if a CF mutation can be identified in either individual.
MSAFP testing will not provide any valuable information on CF. With a known family history, a pedigree analysis may change the absolute numerical risk of having an affected child but it doesn’t change the patient’s concern. Even though this is a relatively “manageable disease”, there are many complicating factors, and since prenatal diagnosis is available, if the patient wants to know the fetal status, she should be given that information. However, before a fetus is testing, you need to know for sure that both parents are carriers. If one is not, then there is no risk to the child. Furthermore, if you cannot detect both mutations in the parents, you will not be able to detect 2 mutations in the fetus, so the assay may be uninformative, in addition to the risk it incurs.
Jenna has a brother, Tom, with a known deletion resulting in Duchenne muscular dystrophy (DMD). Jenna is 16 weeks pregnant and is concerned about whether her fetus will be affected with DMD. Which of the following clinical genetic tests should be done first to provide the most information about this possibility at the least risk to the fetus?
E. Mutation analysis of Jenna’s DNA.
Neither ultrasound nor MFAFP/triple testing will help in the diagnosis of DMD. Karyotype analysis will only be useful if the deletion is large enough to be seen, and most DMD deletions are smaller than that. Molecular testing is the assay of choice, but before doing any invasive fetal studies, it is important to determine if there is a need to incur that risk. In this case, it should be determined that the mother is a carrier. If she’s not, you don’t need to test the fetus.
