Unit 7 - Prenatal Genetics Flashcards
(28 cards)
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
