Prenatal Genetics Flashcards
1
Q
Prenatal Diagnosis
A
- medical evaluation of a fetus- that provides both physical and genetic information
- genetic testing has the capability to diagnose fetal disease
- prior to testing, parents should be counseled about the reasons to do the test and the possible outcomes
- depending on the type of test, there could be a risk to the mom and to the pregnancy
2
Q
Indications for Prenatal Diagnosis-Inherited
A
- familial chromosome anomaly
- family history of a genetic disorder for which testing is available
- Familial X linked recessive disorder without testing available
- increased risk of ONTD (recurrence risk 2-5%)
- carrier of genetic disorder, ethnic risk
- consanguinity
3
Q
Other Reasons for Prenatal Diagnosis
A
- ultrasound anomaly
- repeated miscarriages
- Abnormal MSAFP (maternal serum alphafetoprotein)
- anxiety
- environmental exposures
- increased risk of a chromosomal abnormality
4
Q
Relative Frequency of Types of Aberration
A
- most common live birth anomaly is trisomy 21
- most common aneuploidy is 45,X
- most common autosomal aneuploidy is trisomy 16
- triploidy is the third highest frequency cause of fetal loss
5
Q
Spontaneous termination frequencies
A
- 95% of 45,X conceptions
- 90% of trisomy 12 conceptions
- 80% of trisomy 18 conceptions
- 65% of trisomy 21 conceptions
6
Q
Tests available
A
- examination
- ultrasound
- cytogenetics
- biochemical
- molecular studies
7
Q
invasive vs non-invasive tests
A
- in general, non-invasive is better than invasive- less risk to the fetus
- want the most specific information at the least risk
- types of testing performed depends on clinical indication- and what information needs to be collected
8
Q
Ultrasound
A
- verify viability
- detect a multiple pregnancy
- determines the gestational age
- determine the sex
- identify possible abnormalities
- may indicate that additional studies are needed
- usually performed around 18 weeks
9
Q
Nuchal translucency
A
- indicator on ultrasound of a possible abnormality in a fetus like chromosomal
- thickness of 6.0 mm has been associated with Down syndrome
10
Q
Clefting
A
-unilateral or bilateral cleft lip, cleft palate, or both can be detected on ultrasound and are usually indicators of a genetic defect
11
Q
Neural tube defects
A
- can be detected on ultrasounds
- like a meningomyelocele
- range of severity
- less severe forms may be corrected surgically, more severe can be debilitating
- closed: skin is intact
- open: rupture in the skin (spinal fluid mix with amniotic fluid)
- severe ones like anencephaly- absence of the brain and is lethal
- encephalocele when the brain is extruded from the skull
12
Q
Maternal Serum Alphafetoprotein
A
- 15-20 weeks
- high, low, normal
- gestational age
- mother’s weight, race, diabetic status
- produced by fetal liver and crosses the placenta and can be detected in maternal circulation
- AFP is correlated to the stage of gestation
- risk assessment
- low levels: Down syndrome
- high levels: ONTD- open tubular defects
13
Q
Maternal Serum Quad Test
A
- 4 different substances
- alpha fetoprotein low
- hCG up
- unconjugated estrol low
- dimeric inhibin up
- 80% combined detection for DS
- can be used up to 40 years
14
Q
Integrated Prenatal Testing
A
- 10-13 weeks gestation:
- PAPP-A (pregnancy-associated plasma protein A, when lower associated with increased risk of DS)
- nuchal translucency
- 15-21 weeks gestation the Quad MSAFP testing is performed
15
Q
Non-invasive Prenatal Screening/Testing
A
- the newst non-invasive assay is know as NIPS
- cffDNA= cell free fetal/placental DNA
- isolated from maternal blood at 10-22 weeks gestation
- 10-15% of cfDNA in maternal blood is fetal in origin
16
Q
Technology
A
- sequencing to identify DNA fragments
- determine chromosomal source of each fragment
- statistically analyze the number of fragments per chromosome compared to expected number for mother and fetus
17
Q
Detection of Aneusomy
A
- the expected amounts of DNA per chromosome are analyzed, and any increase or decrease in the total value for a particular chromosome would suggest an aneuploidly
- the numbers are very small, so the hardware and software have to be precise
- it is a screening test that gives a risk for a chromosomal abnormality
- if the numbers are out of bounds it has to be confirmed by a diagnostic test which is usually a karyotype analysis and/or FISH
18
Q
NIPS accuracy
A
- DS (+21) and trisomy 18:99%
- trisomy 13:72-92%
- XX: 98.4%
- XY: 99%
- abnormals should be confirmed
- 0.5-7 failure rate- due to insufficient fetal DNA
19
Q
Amniocentesis
A
- needle inserted through abdomen into the amniotic cavity
- 14-20 weeks gestation- usually done 16-18 weeks, can be done as late as 35 weeks
- risk at 1/200
- test possible- AFAFP, cytogenetics, metabolic assays, molecular diagnostics
20
Q
Low AFP Levels
A
- Trisomies 13, 18, 21
- Mosaic Turner syndrome
- Triploidy
- Unbalanced translocations
21
Q
Elevated AFP Levels
A
- increased risk of ONTD
- acetylcholineesterase is the confirmatory test
- AChE should only be present in amniotic fluid if there is a defect in the neural tube
22
Q
AFP testing is for screening ONLY
A
- confirmatory tests
- elevated AFP associated with ONTD- elevation in acetylcholinesterase in the amniotic fluid
- low AFP- chromosomal disorders, specifically Down Snydrome, karyote analysis
23
Q
Chorionic Villus Sampling
A
- 10-14 weeks gestation
- limb reduction when done <10 weeks
- risk 1/100
- cytogenetics, molecular diagnostics, metabolic (cells only)
- usually works because fetus and placenta come from same zygote (unless mosaicism)- abnormal CVS test may merely mean there is a problem with the placenta
24
Q
Localized Mutation- Placental
A
- -if a mutation occurs only in the layer of cells that will become the placenta, the fetus may be perfectly fine
- all or part of the placenta may carry the mutation
- if only part of the placenta has a mutation, it is called confined placental mosaicism
- a mutation in the placenta may or may not affect the development of the fetus
- if the placenta is sufficiently compromised if may not support fetal development
- if a CVS is done and detects a mutation, it could result in a misinterpretation of the fetal status
25
Confined Fetal Mutation
- if the only cells with the mutation occur in the fetus, then the CVS testing will miss that all together
- this risk is low since this doesn't occur very often, but whenever CVS testing is done early, it is important to continue to monitor the pregnancy
- the fetus may be completely abnormal or only some of the cells may have the mutation
26
Why choose CVS
-if a couple wants to know early if there is a problem so that they have the option of termination of pregnancy, this is the testing method of choice
27
Outcomes of Prenatal Diagnosis
- no anomalies in 98% of cases
- termination
- fetal treatment in utero
- IVF
28
Assisted Reproductive Technologies
- IVF
- intracytoplasmic sperm insertion
- zygote intrafallopian transfer
- donor egg
29
Polar Body Analysis
- polar body can be collected and tested with no ill effects to the oocyte
- a polar body can be collected and tested with no ill effects to the oocyte
- if the 1st polar body tests positive for the CF mutation known to be carried by the mom than the corresponding egg would be expected to have CF mutation
30
Preimplantation Genetic Diagnosis
- polar body analysis is difficult so prenatal genetic diagnosis was developed
- screening technique for embryos
- unsatisfactory = destroyed
- eggs collected and fertilized in vitro, at 8 cell stage a single cell is separated out and tested by FISH or molecular assay
31
Next generation screeening
- replace PGD because it is a whole genome screen
| - 3000-5000 dollars
32
Donor Egg
- one for mitochondria problems, moms nucleus put in donor egg
- or can just carry a donated egg
