Genetic Screening Flashcards
Components of the first trimester screen? Detection rate for Downs?
NT, PAPP-A, free or total HCG
82-87%
Most common aneuploidy in products of conception?
Trisomy 16 (non-viable)
Most frequent monosomy?
Turner’s (Monosomy X)
Most common autosmal aneuploidy in LIVE born infants?
Trisomy 21
When can you perform a NT?
10w0d - 13w6d
What is defined as an enlarged NT?
> /= 3.0 mm
With an enlarged NT what is the likelihood of fetal aneuploidy?
50%
What structures produce AFP?
Glycoprotein secreted by the yolk sac and liver of the fetus
What is the detection rate for open neural tube defects with an elevated maternal serum AFP
65-80%
Is msAFP elevated in CLOSED neural tube defects?
Nope!
At what gestation does the neural tube close?
4 weeks
What other conditions (besides open NTD) are associated with elevated AFP?
- Multiple Gestation
- Fetal abdominal wall defects
- Fetal nephrosis
- Fetal demise
- Placenta conditions that increase risk of adverse outcomes later on in pregnancy
When can you perform cell free DNA testing?
9-10 weeks gestation (until term)
What factors affect the quantity of fetal fraction in cf DNA?
Gestational Age Maternal BMI Med exposure Maternal race Aneuploidy status Fetal or maternal mosaicism Single or multiple gestation
Which screening test in the most sensitive and specific for the common fetal aneuploidies?
cfDNA
> 98-99%
What GA is CVS testing performed?
10w0d-14w0d
Risk of materno-fetal hemorrhage with CVS testing?
14%
What GA is amniocentesis performed?
15w-20w
Risk of materno-fetal hemorrhage with amnio?
2-6%
Give Rhogam!
< 12 wks = 50-120 mcg
> 12 wks = 300 mcg dose
GA for First Trimester Screen + components
10-13w6d
NT, PAPP-A, B-Hcg
GA for Quad Screen + components
15w-22w6d
AFP, BHcg, Estradiol, Inhibin A
Describe integrated screening
“Integrated Screening”: NT + PAPP-A @ 10-13w THEN Quad Screen 15-22w
“Serum Integrated” - same, however no NT US
What is the difference between between Stepwise Sequential and Contingent Screening?
In both first trimester screen is obtained
Stepwise Sequential: low risk does QUAD screen
Contingent: low risk does NO ADDITIONAL tesing
Components of Stepwise Sequential Screening? GA?
First tri screen: NT, PAPP-A, Hcg (10w-13w6d)
Low risk: THEN QUAD (AFP, Bhcg, Estradiol, Inhibin A) 15-22w
High Risk: Diagnostic vs cfDNA
Components of Contingent Screening? GA?
First Tri Screen: NT, PAPP-A, Hcg (10-13w6d)
Low Risk: No testing
Medium: QUAD (15-22w)
High: Diagnostic vs cfDNA
Risk fo Downs Syndrome w/ maternal age > 40
1:51
When a cystic hygroma is identified in the first trimester, what percentage of fetuses are aneuploid?
50%
US Findings:
- Thickened Nuchal Fold
- Echogenic Cardiac foci
- Echogenic bowel
- Short humerus
- Absent nasal bone
Down’s Syndrome
In the second trimester- what is the most sensitive and specific finding for Down Syndrome?
Thickened nuchal fold
Soft markers on US for Downs Syndrome in SECOND trimester?
Echogenic Cardiac Foci Pyelectasis Echogenic bowel Thickened nuchal fold Mild ventriculomegaly Choroid plexus cysts Shortened femur length
What anomalies are associated with an increased NT (> 3 mm)
Aneuploidy
Congenital heart defects
Abdominal wall defects
Diaphragmatic hernies
What percentage of fetuses with increased NT measurement (> 3 mm) will have aneuploidy?
50%
At what gestational age is NT measurement MOST sensitive in screening for aneuploidy?
13 weeks
Quad Screen Results for Down Syndrome?
PAPP-A = low
B-hcg = high
Estradiol = low
Inhibin A= high
DOWN (low) unless they are HI (hcG, Inhibin A)
Findings of “lemon sign” and “banana sign” on ultrasound are most consistent with which of the following congenital anomalies
Open neural tube defect
Tell me about cell free fetal DNA testing
Noninvasive prenatal testing that using cell free fetal DNA from the plasma of the pregnant woman
Detection rate for Trisomy 13/18/21 is > 98% for each
Very low false positive rates < 0.5%
Most sensitive and specific screening test for common aneuploidies
**only screening test that can tell you gender and sex chromosome aneuploidies
Amniocentesis vs CVS
CVS earlier (10-12 wks), can’t measure AFP, tissue specimen, inappropriate for diagnosis of NTD
Amniocentesis (after 15 wks), can measure AFP, samples individual cells, appropriate for NTD detection
How is Fragile X syndrome inherited? Mutation on what gene?
X linked recessive
FMR1 gene
Tri-nucleotide CGG repeats
< 45 repeat unaffected
Intermediate 45 - 54 repeats
Pre-mutation 55-200 repeats
Full mutation > 200 repeats
Occurrence risk of NTD?
*multi factorial (environmental and genetics)
*having family members with condition increases risk
General population 0.3% (400 mcg folate/day)
With one affected child 2-4% (4 g folate/day)
With two affected children 10%
Start 1-3 months prior to conception
‘folate resistant’ NTD?
Folate will NOT prevent them, increased dose not necessary
Valproic acid in first trimester
High fetal glucose levels
First trimester fever or prolonged elevated maternal temperature (sauna use)
Obesity
Is there anytime where an omphalocele would be considered “normal”
YES! Between 9-11 wks gestation (with herniation of the hind gut in normal development)
