Genetics - Prenatal Diagnosis And Treatment

Front 1

Why is prenatal diagnosis performed?

Back 1

due to family hx or carrier testing, advanced maternal age, routine prenatal care,

Front 2

What is the goal of prenatal testing?

Back 2

to inform couples about the risk of a birth defect or genetic disorder

Front 3

What are 7 main indicators for invasive prenatal testing?

Back 3

1. advanced maternal age
2. previous child with de novo chromosomal aneuploidy
3. presence of structural chromosome abnormality in one of the parents.
4. family hx of genetic defect
5. family hx of x-linked disorder with no prenatal test
6. risk of neural tube defect
7. maternal serum screening and ultrasound exam

Front 4

What is a de novo chormosomal aneuploidy?

Back 4

"brand new" - occurred in gameto genesis of the parents.

Front 5

What is an NTD?

Back 5

neural tube defect

Front 6

What are 4 invasive tests done for prenatal diagnosis and screening?

Back 6

amniocentesis
chorionic villus sampling
cordocentesis
preimplantation genetic diagnosis

Front 7

What are 4 ways of non-invasive testing

Back 7

-maternal serum alpha fetal protein
-1st and 2nd trimester
-ultrasonography
-isolation of fetal cells from maternal circulation

Front 8

What is cordocentesis?

Back 8

drawing blood from umbilical cord

Front 9

What is preimplantation genetic diagnosis?

Back 9

Going through eggs produced and choosing which one doesn't have the mutation for invitro fertilization

Front 10

What is amniocentesis?

Back 10

Insertion of a needle into the amniotic sac to remove a sample of fluid that contains cells of fetal origin for culture and analysis

Front 11

Amniocentesis is usually preceeded by, and guided by, ____

Back 11

ultrasound

Front 12

At what point is amniocentesis usually performed?

Back 12

15-16 weeks

Front 13

Amniocentesis tests fetal ____ and concentration of_____ in amniotic fluid.

Back 13

chromosomes (karyotype)
alpha-fetoprotein (AFP

Front 14

____ is produced in the liver, secreted into circulation and excreted through kidneys of a baby in uterus.

Back 14

AFP (alpha-fetoprotein)

Front 15

In what two ways is AFP measured?

Back 15

AFAFP -

MSAFP -

Front 16

AFAFP or MSAFP can measure for likelihood of ______ defect (if highly elevated), or _____ if AFP reduced.

Back 16

1. if elevated - may indicate neural tube defect

2. if reduced - trisomy, esp 21

Front 17

AFP levels can detect 100% of ____

Back 17

anencephalopathy

Front 18

What is the major complication of amniocentesis?

Back 18

1/1600 risk of inducing miscarriage over baseline

Front 19

When are tests other than AFAFP and Karyotype done?

Back 19

only when indicated

Front 20

What is chorionic villus sampling?

Back 20

Biopsy of tissue from villous area of the chorion.

Front 21

When is chorionic villus sampling done?

Back 21

10-12 weeks gestation.

Front 22

What is the major advantage of the chorionic villus sampling?

Back 22

Results done at earlier gestational age.

Front 23

What are disadvantages of chorionic villus sampling?

Back 23

cannot assay AFP,
increased risk to fetus by 1% over baseline due to inc. risk of placenta previa

Front 24

Chorionic villus sampling has same success rate as amniocentesis but higher rate of ____

Back 24

mosaicism (genetic info from mom AND baby, may be a problem)

Front 25

Chorionic villus sampling (does/does not) lead to risk of limb defects in fetus.

Back 25

Does not

Front 26

An open NTD leads to higher concentration of ____

Back 26

AFP

Front 27

There is ______ overlap between NTD and normal, therefore definitive diagnosis requires ____

Back 27

1. considerable overlap
2. ultrasonography

Front 28

What can be done to prevent NTD?

Back 28

periconceptional supplementation with folic acid (reduces risk by 75%- also drops risk of orofacial cleft formation)

Front 29

MSAFP is really important in diagnosing _____ and is obtained/ tested by ____/

Back 29

open neural tube defect -

blood draw from mother (non-invasive)

Front 30

What is the leading indicator for invasive techniques when screening prenatally?

Back 30

advanced maternal age and known risk of aneuploidies

Front 31

Screening being limited to advanced age or known risk of aneuploidy reslutsl in _____.

Back 31

about 70% of trisomies being missed (many born to women <35)

Front 32

What is a partial solution to the lack of aneuploidy screening?

Back 32

MSAFP is done on everyone and may be depressed in many trisomic pregnancies.

Front 33

Aneuploidy screening (is/is not) a definitive diagnosis.

Back 33

IS NOT

Front 34

_____ involves a battry of maternal serum markers that have been developed to use in conjunction with ultrasound.

Back 34

Aneuploidy Screening.

Front 35

First trimester aneuploidy screening relies on what?

Back 35

-quantifying levels of certain substances in the serum (PAPP-A and hCG)
- measurng subcutaneous edema of fetal neck

Front 36

What is PAPP-A?

Back 36

Pregnancy Associated Plasma Protein A

Front 37

What is hCG?

Back 37

human Chorionic Gonadotropin

Front 38

What is nuchal translucency?

Back 38

Thickness of echo free space between skin and soft tissue overlying dorsal aspect of cervical spine

Front 39

Nuchal translucency is bigger in ))))

Back 39

trisomies, and 45,X fetuses (single X aka Turner's)

Front 40

First trimester aneuploidy screening has ____ sensitivity?

Back 40

~84%

Front 41

In second trimester screening, triple screen includes _____.

Back 41

MSAFP, free B-hCG, and uncongugated estriol

Front 42

In second trimester screenng, quadruple screen includes ____

Back 42

MSAFP, free B-hCG, and uncongugated estriol, and inhibin A

Front 43

Aneuploidy screening in the second trimester has detection rates of ___ in the triple screen and ___ in quadruple screen for autosomal trisomies

Back 43

72 (triple)
81 ( quadruple)

Front 44

If aneuploidy screening results in likelihood of abnormality, the mother may do ____ _for confirmation.

Back 44

invasive

Front 45

____ screening means the risk is reduced but doesn't rule out NTD or trisomy

Back 45

negative aneuploidy screening

Front 46

High resolution, real time ultrasound scanning is important for:

Back 46

assessment of fetal age, multiple pregnancies,
fetal viability
adetection of morphological abnormalities

Front 47

Ultrasound testing for single gene disorders may be used when _____ is unavailable.

Back 47

blood or tissue sample

Front 48

What must you have for ultrasonography testing for single gene disorders?

Back 48

Well-defined phenotypic abnormality to go along with mutation

Front 49

What is one great example of a single gene disorder that could be picked up on ultrasound>

Back 49

Holt-Oram Syndrome: (autosomal dominant with congenital heart defects and evident hand abnormalities)

Front 50

_____ may be used when risk is uncertain due to lack of family history and testing. (ex, prior preg had stillbirth with features of osteogenesis imperfecta - next baby may have this test to discern likelihood)

Back 50

ultrasonography testing

Front 51

What types of multifactorial disorders can be identified by ultrasonography?

Back 51

Some isolated abnormalities that recur in families such as some NTDs, some heart defects.

Front 52

When is ultrasonography to determine fetal sex performed?

Back 52

15+ weeks

Front 53

What is one use for fetal sex ultrasonography?

Back 53

diagnosis of X-linked disorders

Front 54

____ could be used for short-term incubation karyotyping.

Back 54

Chorionic Villi Sampling

Front 55

What is FISH screening?

Back 55

Fluorescence analysis screening for common aneuploidies that can happen soon after amniocentesis (may take only 1-2 days)

Front 56

What is cytogenetics?

Back 56

Fetal cells for karyotyping are used for biochemical or DNA analysis.

Front 57

How long does a cytogenetic culture and analysis take?

Back 57

7-10 days

Front 58

Where do cells for Cytogenetic testing come from?

Back 58

CVS or amniocentesis

Front 59

Chromosome abnormalities are more likely identified when fetus has ____

Back 59

multiple physical malformation

Front 60

What are the most common abnormal karyotypes?

Back 60

trisomies, turner syndrome, or unbalanced structural abnormalities

Front 61

What is mosaicism?

Back 61

Presence of two or more cell lines in an individual or tissue sample

Front 62

What is clinical significance of DNA mosaicism?

Back 62

a person may have different types of DNA. Ex) ovaries can have genes of absorbed twin and not "genetically" the same as whole woman

Front 63

What complications may have problems in the fetus with mosaicism?

Back 63

May be diploid and haploid DNA that don't combine correctly

Front 64

What are the three basic levels of mosaicism ?

Back 64

True mosaicism, pseudomosaicism, and inconclusive

Front 65

What is true mosaicism?

Back 65

Multiple colonies from several different primary cultures. (several tissue samples show mosaicism) - fetus likely actually mosaicism

Front 66

What is pseudomosaicism.

Back 66

Only one cell in a single sample shows mosaicism - usually disregarded as a misake

Front 67

Mosaicism in several cells or colonies in a single primary culture -

Back 67

difficult to interpret, may be mistake and regarded as pseudomosaicism, but may suggest small likelihood of true mosaicism.

Front 68

______ may be responsible for some cases of mosaicism when XX and XY cells are present.

Back 68

Maternal cell contamination

Front 69

Maternal cell contamination is more common in ____, and when suspected may recommend ____

Back 69

1. CVS
2. may recommend amniocentesis

Front 70

What is confined placental mosaicism?

Back 70

Mosaicism present in placenta but absent in fetus.

Front 71

What does confined placental mosaicism suggest?

Back 71

Trisomy rescue.

Front 72

What is trisomy rescue?

Back 72

Cells spontaneously reject trisomic chromosome and bring it back down to a disomy (normal).. but don't necessarily split mom and dad - may keep 2 from mutant cell.

Front 73

What are some of the most difficulty challenges with chromosome analysis?

Back 73

Confirming and interpreting mosaicism - may be a ton of possibilities.

Front 74

What is culture failure?

Back 74

Cell cultures die, don't grow, etc

Front 75

When CVS culture fails, there is time for ____

Back 75

amniocentesis.

Front 76

When can cordocentesis be performed?

Back 76

18 weeks gestation

Front 77

____ can be a concern when time is critical

Back 77

culture failure

Front 78

>100 disorders can be diagnosed in cultured fetal cells by_____

Back 78

biochemical assays

Front 79

Most disorders found in _____ are rare in population but more likely (25%) recurrence among siblings

Back 79

biochemical assays

Front 80

What is one advantage of Biochemical assays over DNA analysis?

Back 80

DNA analysis only accurate for detection of the mutation being tested for, but biochemical testing can detect any abnormality that affects the protein.

Front 81

For biochemical assays, each specific disorder may have a ____

Back 81

separate specialized laboratory center

Front 82

DNA analysis is done through _____ or use of ____

Back 82

direct mutation or use of closely linked markers

Front 83

Direct methods of detection for mutations are preferable in _______.

Back 83

DNA analysis

Front 84

Effectie prenatal therapy is not available for most disorders, and some parents may decide _____ based on results.

Back 84

Terminate pregnancy

Front 85

What is the principal advantage to a family receiving this prenatal genetic testing?

Back 85

Parents can undertake pregnancies with the early knowledge the fetus has an abnormality.

Front 86

Elective abortions occuring due to genetic concerns is ______ of all elective abortions

Back 86

A very small portion

Front 87

Prenatal treatment is used when?

Back 87

When prenatal diagnosis detects genetic defects or disorders with available treatment options

Front 88

When is prenatal treatment most successful?

Back 88

metabolic disorders treated through maternal medial therapy

Front 89

Prenatal bone marrow transplants (have/have not) been successful.

Back 89

HAVE