Genetics Flashcards
What are considerations for genetic testing in women > 40?
Discuss risk of pregnancy loss, screening for aneuploidy (discuss NIPT or cfDNA), invasive testing for aneuploidy. Carrier screening (SMA, CF, etc). Genetic counseling.
What is cell free DNA?
Identification of fetal fraction of DNA from fetal blood cells in the maternal blood circulation. This helps detect aneuploidy. Performed after 10 weeks. Sensitivity for is >97%. Limitation of use in obesity.
- detects T13,18,21, sex chromosome aneuploidy, Rh status.
What is an omphalocele?
- occurs 1:5000
Omphalocele is a midline defect in which bowel and other organs are exteriorized but covered by a membrane. Associated with increased risk of aneuploidy. Can be delivered vaginally. - liver herniation
- NORMAL in embryo (physiologic gut herniation from 8-12wks)
What is gastroschisis?
open abdominal wall defect, bowel contents exposed to amniotic fluid. occurs 1:2500 (vs 1:5000 w/ omphalocele)
- Defect occurs slightly to the right of the midline (right paraumbilical)
- Delivery via CS (mostly if other organs also extruded due to risk of injury).
What are considerations for someone with Jewish ancestry?
Screen for fam hx for inherited disorders: metabolic disorders, Fanconi’s anemia, CF, Tay-Sachs.
What would you do if she’s a carrier for Tay Sachs? Her husband should be tested since its AR.
What is defect in Tay Sachs? ?? polysaccharide
What are details about Trisomy 21?
What is patient’s risk of having child’s with T21? Her risk is higher that of average woman.
What testing options would you discuss? cfDNA. She could undergo testing herself. Invasive testing (CVS, amnio).
What US findings would suggest T21? Cardiac anomalies (ASD, VSD, TOF), duodenal atresia (double-bubble sign), skeletal anomalies (short femur), absent nasal bone
What abnormalities on cytogenetics? occurs 2/2 Unbalanced translocation of T21 (5%)
incr risk SAB, PTD, FGR, IUFD. and hDP for mom!
At what crown rump length should you perform a nuchal translucency?
45-84mm.
What is a nuchal translucency and when do you perform it?
Perform NT between 11w0d and 13w6d
normal is <3mm.
Offered to all pregnant women as screen for aneuploidy.
NT is echo free area at back of fetal neck seen by US
Larger the NT the higher the fetal risk
Increased nT increases risk of aneploidy and fetal anomalies (cardiac and abdominal wall defects)
Aneuploidy detection rate 64-70%.
How do you manage thickened NT and what can cause false elevations?
Sonographer technique.
I would first review the chart, see if prior genetic testing, take a detailed history, and counsel the patient on the US findings.
Can do CVS between 10-13wks, cfDNA after 10w, 1st trimester screen 10w-13w6d, quad screen 15-22w6d, amnio after 15w,
What is quad screen?
Reports AFP, estriol, inhibin, HCG as multiples of the mean.
Done between 15-22 weeks. Has 80% detection rate for T21 and 60-70% for T18 and 80% NTD. If you do 1st trimester screen, only need to do MSAFP component of quad screen.
What is pattern for T21? Hi!!! HCG and inhibin elevated. Estriol and AFP low
What is pattern for T13? Can’t be detected on quad screen.
What is pattern for T18? Everything is low.
What causes false positive quad screen? Vanishing twin, inaccurate dating.
Compared to CVS, amnio has what advantages?
Amnio has less risk of confined placental mosaicism and maternal cell contamination.
- Amnio can also detect neural tube defects which can’t be detected on CVS.
- If do NIPT, also also AFP (component of quad screen) bc NIPT can’t detect neural tube defects.
CVS pregnancy loss risk 1:200
Amnio pregnancy loss risk 1:400
Causes of elevated AFP?
If unexplained elevation in AFP, what is pregnancy at risk of?
Elevated AFP is >2.5 MoM
Open neural tube defects, chromosomal disorders (triploidy), multiple gestation, abdominal wall defects (gastroschisis), chorioangioma, incorrect dating
IPD (HDP, abruption, PTB, FGR), oligohydramnios, IUFD.
Do amnio to confirm diagnosis of neural tube defect: will also show you acetylcholinesterase.
What is Chiari malformation?
What is the lemon sign
What is the banana sign?
Can have lemon and banana signs. Arnold-Chiari II is when cerebellum pushes into spinal cord. associated with spina bifida 2/2 herniation of cerebellar vermis through foramen magnum.
- lemon sign: frontal bossing or flattened frontal contours of fetal skull, resembling shape of lemon
- banana sign: posterior convexity of the cerebellum resembling shape of cerebellum.
What are soft markers for aneuploidy?
Dilated lateral ventricles, thickened nuchal translucency, Choroid plexus cysts, renal pelvis dilation, absent nasal bone, echogenic intracardiac focus, echogenic bowel, short femur, increased nuchal fold (<6mm).
Cystic hygroma (increased NT along length of fetus w/ septations): assoc w/ chromosomal abnormalities in 55% (mostly T21, T18 and Turner’s)
What are 2nd trimester markers for down syndrome?
Absent nasal bone, duodenal atresia (double bubble sign), cardiac anomalies (AV canal defect), short femur. Most significant is thickened nuchal fold. What does nuchal fold suggest? aneuploidy, fetal anomalies (Cardiac)
Structural abnormalities associated with T13?
holoprosencephaly=most common. Polydactyly, cleft-lip, NTD, cardiac defects, omphalocele, incr NF.
Structural abnormalities associated with T18?
Rocker bottom feet, clenched fists, meningomyelocele, omaphalocele, cystic hygroma, nuchal thickness, polyhydramnios, cardiac defects, renal anomalies, fGR, choroid plexus cysts.
What is an AV canal defect?
Atrium are connected and ventricles are connected. Failure of the endocardial cushion to develop. Issue with neural crest migration.
Quad screen with estriol of <0.15 MoM. exam reveals ambiguous genitalia and symbrachydactyly. What is most likely diagnosis?
Smith-Lemili-Opitz syndrome: mutation in chromosome 11, causes lack of cholesterol production. Has syndactyly of 2nd and 3rd toes, ambiguous genitalia and other anomalies of internal organs.
What are causes of low estriol on a quad screen?
Incorrect dating, IUFD, Smith-Lemli-Opitz syndrome, steroid sulfatase deficiency.
