Flashcards in Chapter 7: Genetics Deck (23)
Heteroploidy: Alteration in chromosome number
What is Euploidy? Provide the common subtype and what they lead to as far as pregnancy
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
What is Aneuploidy?
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
What is Trisomy 21 and what weird genetic change can predispose you to it?
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)
Prognosis/frequency of Downs and how it presents
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
Prognosis and frequency of Trisomy 18
Edwards: 1:8,000: Severe mental retardation, multiple organ abnormalities, less than 10% survive one year
Prognosis and frequency of Trisomy 13
Patau Syndrome: 1:20,000: Severe mental retardation. Neurologic, ophthalmologic, and organic abnormalities. 5% survive 3 years
Discuss the effect of Trisomy 16
0 live births. Lethal anomaly occurs frequently in first trimester spontaneous abortions. No infants can have this.
What causes sex chromosome abnormalities? How common are they?
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.
Discuss the findings and frequency for 45X Syndrome
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.
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
What causes Cri-du-chat and what does it look like
Cri du chat - del(5p) = Severe mental retardation, microcephaly, distinctive facial features, characteristic "cat's cry" sound
Mitochondrial mutation inheritance pattern
All your organelles are from mom's egg. Dad just gives DNA via sperm.
What four risk factors do we see for genetic issues?
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
Screening test vs diagnostic test
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.
As a recap from chapter 6, what do we screen for in each trimester?
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
First trimester screening is all about screening for risk of Down syndrome, Trisomy 18 and Trisomy 13. What are we looking for?
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
What do we do during second trimester tests?
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)
Two ways we can test for carrier status
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.
Three ways to test the fetus
Chorionic Villus Sampling
Percutaneous Umbilical Blood Sampling
Discuss Amniocentesis and risks
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.
Discuss Chorionic Villus Sampling and risks
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.