Prenatal Cytogenetics Flashcards
Incidence of aneuploidy in sperm, oocytes and preimplantation embryos?
1-2% sperm, 20% oocytes and 20% preimplantation embryos
4 common aneuploidies (35%) of spontaneous abortions?
45, X, +16, +21, +22
3 common aneuploidies (4%) of stillbirths?
+13, +18 and +21
6 common aneuploidies of live births?
+13, +18 and +21
XXX, XXY (Klinefelters), XYY (Jacobs)
Risk of recurrent aneuploidy?
1-1.5% until AMA
True of false? 45, X associated with AMA
False, paternal risk
Young maternal age range risk for aneuploidies
13 to 20
3 risks with advanced paternal age (APA)?
- Structural abnormalities
- Point mutations (achondroplasia)
- Schizophrenia or mental illness
Risk for aneuploidy at 20, 35 and 41?
1 in 1152, 1 in 240 and 1 in 41 (first trimester Down syndrome)
Protein complex degraded in AMA and prolonged prophase arrest?
cohesin
Nuchal translucency increased at ______ mm and measured at _______ to ______ weeks
2.5 mm (or 3), 11-14 weeks
Absent nasal bone marker more common in which population?
Afro-Carribean
Echogenic cardiac focus marker more common in which population?
Asians
Likelihood ratio for echogenic intracardiac focus marker?
1.7
Likelihood ratio for echogenic bowel and cystic fibrosis/placental bleed?
6.7
Up to 48% of fetuses with ________ anomaly will have a chromosome anomaly
cardiac (think aneuploidy, Noonan, 22p11.2)
Triploidy incidence and % of pregnancy loss
1 in 1000, 8-10% of pregnancy loss
Complete mole karyotype and entirely _________ (maternally, paternally) derived
46, XX (90%) or 46, XY (10%) (90% two sperm, 10% diploid sperm) and paternally
- no embryo
- hydropic villi
Complete mole risk for trophoblastic disease and choriocarcinoma
trophoblastic disease - 15-20%
choriocarcinoma - 2-4%
Incomplete mole karyotype and risk of gestational trophoblastic disease and preeclampsia
69
4% risk of trophoblastic disease
35% risk of preeclampsia
Incomplete moles are most commonly caused by diploid ______ fertilized by _______ sperm
Diploid egg, haploid sperm (30-40% of cases)
69,XXX (37%) or 69,XXY (60%) or 69,XYY (3%)
Year for first amniocentesis with karyotype?
1956
Year for chorionic villous sampling?
1983
Year for first chromosomal microarray (CMA)?
2010
Year for cell free NIPT?
2011
Year for prenatal WES or WGS?
WES - 2013
WGS - 2017 (not commercially available)
_____ ________ ________ is when the placenta has chromosome anomaly while fetus is unaffected (0.8-2% at 8-11 weeks)
confined placental mosaicism (CPM)
Maternal and NIPT are ______________ tests
screening tests
amniocentesis, CVS and cord blood are ___________ tests
diagnostics
On maternal serum screening trisomy 21 is associated with increased?
hCG and inhibin A
On maternal serum screening neural tube defects are associated with increased?
AFP
cfDNA in NIPT is ~ ______ bp in length
200
NIPT performed after _______ weeks
10
NIPT may use either ____________ sequencing or ___________ sequencing
random, targeted (SNP cannot tell homozygosity from deletion)
NIPT abnormalities detected?
- Trisomies (+13, +18, +21)
- Sex chromosome anomalies 45, X/47, XXX/ 47, XXY/ 47, XYY
- Triploidy
PPV in NIPT is only about 90% for which 3 disorders?
+21, +18, sex chromosome abnormalities
*also depends on age (as prevalence changes)
3 reasons for false positive NIPTs?
- CPM - confined placental mosaicism
- Reabsorbed twin
- Maternal conditions
2 reasons for false negative NIPTs?
- Fetal mosaicism
- Partial trisomy
4 Maternal causes of NIPT no call
- obesity (too many maternal cells)
- anticoagulation
- B12 deficiency
- maternal cancer
- maternal bone marrow transplant
3 Fetal causes of NIPT no call
- Twin demise
- Triplets
- GA too early
Sensitivity for trisomy 21 first and second trimester serum screening as well as combined?
85% first trimester
81% second trimester
95% combined
False positive rate for trisomy 21 by serum screening and NIPT?
serum - 5%
NIPT - 1%
Amniocentesis is performed after __________ weeks
15.5
Amniocentesis miscarriage risk:
1/200 to 1/1000
Amniocentesis risk after 24 weeks
Preterm delivery
3 uses of amniocentesis
- Genetics
- Fetal lung assessment
- Remove excess fluid
Chorionic villous sampling performed between _______ and _______ weeks
11-14 weeks
CVS risk
1 in 100 to 1/1000
Umbilical cord/cordocentesis performed at _______ to _______
17-20 weeks
Miscarriage risk ____ to _____ % for cordocentesis/umbilical cord sampling
1-7%
5% of couples with _____+ miscarriages/anomalous pregnancies have a chromosome rearrangement
3 miscarriages
Maternal cell contamination/gestational cell contamination source in CVS?
Decidua contamination in CVS (1-2%)
