Unit 7 - Prenatal Genetics Flashcards
what are inherited indications for prenatal diagnosis?
- familial Xm anomaly
- FH of genetic disorder where testing is available
- XLR disorder w/o testing available
- increased risk of ONTD (recurrence risk 2-5%, population risk 1/500-1/1000)
- carrier of genetic disorder or ethnic risk
- cosanguinity
what are non-inherited indications for prenatal diagnosis?
- ultrasound anomaly
- repeated miscarriages
- abnormal MSAFP
- anxiety
- environmental exposures
- increased risk of Xmal abnormality
what is the most common live born Xm anomaly? most common aneuploidy live-born? most common aborted Xm anomaly?
- trisomy 21
- 45,X
- trisomy 16
what are the most common reasons for spontaneous termination frequencies?
95% of 45,X conceptions
90% of trisomy 13 conceptions
80% of trisomy 18 conceptions
65% of trisomy 21 conceptions
what are the 2 major non-invasive tests available? the 3 major invasive tests?
NI: examination and ultrasound
I: cytogenetics, biochemical, and molecular studies
what can ultrasound be used for?
usually performed around 18 weeks gestation
- verifies viability
- detects multiple pregnancy
- determines gestational age and sex
- identifies possible abnormalities
- may indicate additional studies are needed
what anomalies can ultrasound find?
- nuchal translucency - may be associated with Xm anomaly
- clefting - unilateral/bilateral, palate/lip (usually multifactorial)
- NTDs
what is nuchal translucency?
indicator of possible fetal abnormality
-normally 1.3 mm thick, but abnormal if >2.9 mm (Down syndrome associated with 6 mm width)
what are the ranges of severity of NTDs?
- spina bifida occulta (gap in back starting to form)
- meningocele (gap has fluid in it)
- myelomeningocele (spinal cord has come into gap)
closed - skin is still intact, so more possibility for repair
open - rupture in skin exposes neural tube, so spinal fluid mixes with amniotic fluid
what is MSAFP? when is it measured? does this diagnose or assess?
maternal serum alphafetoprotein
- albumin-like PRO made by fetal liver that crosses placenta to be detected in maternal circulation
- measured from 15 to 20 weeks in non-invasive manner
- only for risk assessment
what is important to keep in mind when measuring MSAFP? what do low VS high levels mean?
- gestational age
- mother’s weight, race, and diabetic status
- there is a curve of normalcy, so if don’t take this into consideration, the ranges overlap
- -low: Down syndrome and other Xmal abnormalities
- -high: open spina bifida (ONTD)
what is the maternal serum quad test? are levels increased or decreased in Down syndrome?
measures 4 different substances
- AFP - decreases
- hCG - increases
- uE3 (unconjugated estriol) - decreases
- dimeric inhibin A (glycoprotein hormone secreted by placenta and fetus) - increases
what are the age ranges for MSAFP VS maternal serum quad test?
MSAFP up to age 35, but MSQT up to 40 years
what is integrated prenatal testing?
10-13 gestation week testing for:
- PAPP-A (pregnancy-associated plasma PRO A; when decreased, associated with increased DS)
- nuchal translucency
15-21 weeks gestation week testing for:
- MSQT
- MSAFP
what is non-invasive prenatal screening/testing? is this a diagnostic test or a screening test?
NIPT/S samples mother’s blood at 10-22 weeks gestation
- cell-free fetal/placental DNA is obtained (not the DNA in cells)
- -10-15% of cfDNA in maternal blood is fetal in origin
- use sequencing to identify DNA fragments and determine Xmal source of each fragment, and see if there is a difference from expectancy
- this is a diagnostic test, NOT a screening test
how does NIPT/S detect aneusomy?
if trisomy, there will be a 0.05% increase in total fetal DNA for a particular Xm
NIPT/S accuracy? compared to MSAFP and MSQT?
99% accuracy for trisomy 21 and 18, XY (false positive 0.2%)
72-92% accuracy for other trisomies (false positive 1%)
98.4% XX
0.5-7% failure rate, but still more specific and accurate than serum screening
what is amniocentesis?
invasive test done at 16-20 weeks (wider range from 14 to 20, but risk if not enough amniotic fluid)
- needle inserted through abdomen into amniotic cavity
- risk of fetal loss: 1/200
why can early amniocentesis cause problems?
if done from 13-14 weeks, there is less fluid in amniotic cavity
- loss of fetal mobility causes developmental defects
- -contractures, intrauterine growth retardation
what is AFAFP? is this invasive or noninvasive?
invasive retrieval of amniotic fluid alphafetoprotein
-AFP level rises during gestation, then declines, like in MSAFP
what are low levels of AFAFP related to/
- trisomies 13, 18, 21
- Turner syndrome
- triploidy
- unbalanced translocations
is MSAFP VS AFAFP positive in…
- open NTD
- closed NTD
- multiple pregnancy
- monozygotic twin pregnancy
- fetal death
- body wall defect
- anencephaly
- small mother
- both
- MS, + AF (b/c no mixing)
- MS, - AF (b/c have separate sacs)
- both
- both
- both
- ++ both
- MS, - AF (due to higher concentration)
what is the confirmatory test of elevated AFP levels if looking at increased risk of ONTD?
acetylcholinesterase test
-should only be prsent in amniotic fluid if there is a defect in the neural tube
what is the confirmatory test of low AFP levels if looking at increased risk of Down syndrome?
karyotype analysis to see if Xm abnormality
what is chorionic villus sampling? can AFP tests be done?
invasive procedure done transabdominally or transvaginally between 10 to 12 weeks gestation
- fetal loss 1:100
- risk of limb reduction if done < 10 week gestation
- no AFP measurement b/c no fluid is collected
what is the confirmatory test for abnormal CVS (chorionic villus sampling) results?
amniocentesis
what would complete mosaicism mean for CVS results? localized placental mutation? confined fetal mutation?
remember that CVS relies on both placenta and fetal cells being the same
- CVS will notice mosaicism
- false + b/c fetus is okay
- false - b/c placenta is okay
what is polar body analysis? (example with cystic fibrosis)
when you look at the first polar body of an oocyte to see if the eventual egg will be safe
- if the 1st polar body has the CF gene, then the egg is viable and safe
- if the 1st polar body doesn’t have the CF gene, then the egg has the CF gene and is not safe
