MCM 2-38 Prenatal Genetics

Question 1

goal of prenatal genetics?

Answer 1

help mothers/families make decisions about pregnancies based on family medical history, knowledge of relevant disorders, possible outcomes, and options available to them.

Question 2

families may need information both before and after testing, and it must be

Answer 2

supportive, confidential, and non-directive (family must decide for themselves)

Question 3

indications for prenatal diagnosis include

Answer 3

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

Question 4

ONTD’s

Answer 4

open neural tube defects including spina bifida

Question 5

ultrasound show be used when during pregnancy?

Answer 5

throughout pregnancy to get information about embryo and to follow devlopment/catch any abnormalities

Question 6

Alpha-Fetoprotein Testing (AFP testing)

produced where?

when does it peak?

what effects the expected level?

low levels suggest?

high levels?

Answer 6

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)

Question 7

describe quad screening

detects what?

when used?

Answer 7

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

Question 8

hCG and downs?

Answer 8

increased levels suggest downs

Question 9

unconjugated estradiol (uE3) and downs?

Answer 9

decreased levels suggest downs

Question 10

dimeric inhibin A levels and downs?

Answer 10

increased levels, suggest downs

Question 11

integrated testing

when?

Answer 11

between weeks 10 and 13

nuchal translucency (ultrasound test) and pregnancy associated plasma protein A (decreased levels suggest downs)

Question 12

pregnancy associated plasma protein A levels and downs?

Answer 12

decreased levels suggest downs

Question 13

Non-Invasive prenatal screening (NIPS)

how is it done?

what are the limitations?

Answer 13

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)

Question 14

amniocentesis

when used?

risk?

subsequent tests?

Answer 14

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)

Question 15

Chorionic Villi Sampling

risk?

advantage?

Answer 15

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.

Question 16

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.

Answer 16

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.

Question 17

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.

Answer 17

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.

Question 18

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?

Answer 18

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.