Chapter 7: Genetics

Question 1

Heteroploidy

Answer 1

Heteroploidy: Alteration in chromosome number

Question 2

What is Euploidy? Provide the common subtype and what they lead to as far as pregnancy

Answer 2

Euploidy: Haploid number of 23 chromosomes is altered

Most common subtype:
Triploidy, 69XXX – Results from double fertilization of a normal haploid egg or from fertilization by a diploid sperm

Such things usually end with partial hydatidiform moles and end spontaneously in the first trimester

Question 3

What is Aneuploidy?

Answer 3

Aneuploidy (an-euploidy, literally, not euploid, i.e., the issues will not have “ploid” in the name) – Diploid number of 46 chromosomes altered. TriSOmies are triplicates of one chromosome, not all of them. Most trisomies result from maternal meiotic nondisjunction, which occurs more as a female ages

Question 4

What is Trisomy 21 and what weird genetic change can predispose you to it?

Answer 4

Trisomy 21 (Down Syndrome) – Increased chance if mom or dad has Robertsonian Translocation (where you have translocations that don’t alter the genetic material, you just have the centromere located away from the center of the chromosome = phenotypically normal but you’ll increase chance that offspring will have issues)

Question 5

Prognosis/frequency of Downs and how it presents

Answer 5

1:800 live births. Moderate to severe mental retardation, characteristic facies, cardiac abnormalities, increased incidence of respiratory infections and leukemia. Only 2% live beyond age 50

Question 6

Prognosis and frequency of Trisomy 18

Answer 6

Edwards: 1:8,000: Severe mental retardation, multiple organ abnormalities, less than 10% survive one year

Question 7

Prognosis and frequency of Trisomy 13

Answer 7

Patau Syndrome: 1:20,000: Severe mental retardation. Neurologic, ophthalmologic, and organic abnormalities. 5% survive 3 years

Question 8

Discuss the effect of Trisomy 16

Answer 8

0 live births. Lethal anomaly occurs frequently in first trimester spontaneous abortions. No infants can have this.

Question 9

What causes sex chromosome abnormalities? How common are they?

Answer 9

Sex chromosome abnormalities occur in 1:1000 births. Most common: 45X, 47XXY, 47XXX, 47XXY and mosaicism (presence of two or more cell populations with different karyotypes). Occur due to maternal or paternal nondisjunction.

Question 10

Discuss the findings and frequency for 45X Syndrome

Answer 10

Turner’s Syndrome: 1:10,000: Occurs frequently in the first trimester and often results in spontaneous abortions. Those born are not mentally retarded, but do have lower IQs.

Question 11

Discuss Klinefelter’s

Answer 11

47XXX/XYY/XXY: Klinefelter’s: Each approximately 1:900 chance of happening. Tall, eunuchoid body habitus and small testes. Tall is usually the XYY individuals

Question 12

What causes Cri-du-chat and what does it look like

Answer 12

Cri du chat - del(5p) = Severe mental retardation, microcephaly, distinctive facial features, characteristic “cat’s cry” sound

Question 13

Mitochondrial mutation inheritance pattern

Answer 13

Maternal

All your organelles are from mom’s egg. Dad just gives DNA via sperm.

Question 14

What four risk factors do we see for genetic issues?

Answer 14

a. Advanced Maternal age: Chromosomal abnormalities increase with age, even though the majority of Down Syndrome moms are younger than 35
b. Previous pregnancy affected by chromosomal abnormality
c. History of early pregnancy loss, with at least half of these pregnancies lost to chromosome issues
d. Increased paternal age after 50 for X-linked disorders like neurofibromatosis, achondroplasia, Apert Syndrome, Marfan syndrome

Question 15

Screening test vs diagnostic test

Answer 15

a. Screening vs. diagnostic test: Screening assesses risk of having something. Diagnostic confirms or rules it out. We do diagnostic tests after positive screening tests
i. Ex: Nuchal lucency on US is a screening test. Diagnostic would be genetic karyotype.

Question 16

As a recap from chapter 6, what do we screen for in each trimester?

Answer 16

1. First trimester: 10-13 weeks: PAPP-A, B-hCG, US for nuchal.
2. Second: 15-20 weeks: Triple (maternal serum AFP, estriol, hCG) or Quad (Triple + inhibin)
   a. You can also do first and second at once during second trimester
3. Third: Glucose challenge test, GDM (24-28 weeks), GBS (35-37 weeks), and potential re-screening for Rh antigens and HIV

Question 17

First trimester screening is all about screening for risk of Down syndrome, Trisomy 18 and Trisomy 13. What are we looking for?

Answer 17

ii. Down: Decreased uE3 and AFP. Increased B-hCG and Inhibin A
1. Nuchal transparency at 10-14 weeks: 64-70% by itself. With the other biochemical tests above, goes to 82-87% with a 5% FP rate

iii. Edwards (18): Decreased uE3, AFP, B-hCG and Inhibin A
iv. NTD: Normal uE3, B-hC, Inhibin A, and increased AFP

Question 18

What do we do during second trimester tests?

Answer 18

Second trimester: Triple and Quad screen and also US for gross anatomical changes like cardiac defects and soft markers for Downs (Mild ventriculomegaly, Pyelectasis, shortened femur/humerus)

Question 19

Two ways we can test for carrier status

Answer 19

We don’t have direct testing options for everything, i.e., we don’t have DNA blueprints for everything like we do for Tay-Sachs, hemophilia A, Cystic Fibrosis, and Sickle Cell. Sometimes we have to do indirect testing by looking at restriction fragment length polymorphisms that show a length of DNA that is linked to a condition.

Question 20

Three ways to test the fetus

Answer 20

Amniocentesis
Chorionic Villus Sampling
Percutaneous Umbilical Blood Sampling

Question 21

Discuss Amniocentesis and risks

Answer 21

Amniocentesis: Withdraw 20-40mL transabdominally with US guidance using a 20-22 gauge needed, usually done between 15 and 20 weeks.

Risk of loss is less than 1% with a 99% accuracy. Chorioamnionitis in 1:1000 patients. Prior to 15 weeks has a much higher rate of pregnancy loss.

Question 22

Discuss Chorionic Villus Sampling and risks

Answer 22

Chorionic Villus Sampling: Performed after 10 weeks, transabdominally or transcervically to reach chorionic villus (immature placenta). Can not assess amniotic fluid so not good for NTDs. 32% chance of spotting but otherwise similar risk as midtrimester amniocentesis.

Question 23

Discuss cordocentesis and why we still use it

Answer 23

PUBS: Cordocentesis. After 20 weeks gestation usually just for fetal blood analysis for Rh and cytogenetic/DNA analyses. Rapid fetal karyotypes (18-24 hours and show a picture of the chromosomes in metaphase compared to their homologues, faster due to these cells being in metaphase so you don’t need to culture them first like in amniocentesis) but declining in use.

FISH shows labeling of specific gene changes, and is being added to the karyotype with SKY (spectral karyotyping). CGH (comparative genomic hybridization) looks at VERY small deletions and changes.