Prenatal I

Front 1

Omphalocele has what likelihood of being assoc. with other genetic defects?

Back 1

40%
Recommendations: do chromosomes, Beckwith-Wiedemann, etc.

Front 2

Most frequent conditions assoc. with cystic hygroma?

Back 2

Turner
tri 21
tri 18
tri 13

Front 3

What is the cut-off measurement for nuchal skin fold thickness?

Back 3

More than 6=high risk

Front 4

What is pyelectasis and what could it indicate?

Back 4

Excess fluid in kidneys
Assoc. with increased risk of Down by 1.5 X

Front 5

"Soft signs" of Down syndrome

Back 5

pyelectasis
Duodenal atresia (double-bubble)
ventricular septal defect
choroid plexus cysts

Front 6

2nd trimester genetic sonogram picks up what % of Down?

Back 6

93%

Front 7

Inheritance of Multicystic Dysplastic Kidney?
Inheritance of infantile polycystic kidney?

Back 7

Usually sporadic
AR

Front 8

What maternal problem can cause sirenomelia?

Back 8

poorly-controlled insulin-dependent diabetes

Front 9

Normal time to perform amniocentesis

Back 9

16-18 weeks

Front 10

Early amniocentesis (11-14 weeks) is assoc. with what defects?

Back 10

club foot, miscarriage

Front 11

Name a condition that can be picked up on CVS but NOT amnio?

Back 11

OI (collagen present in placenta cells, not in amniocytes)

Front 12

What if you see choroid plexus cysts on ultrasound?

Back 12

Requires further observation. NOT enough to indicate amnio on its own. (Seen often in tri 18, but may be normal)

Front 13

Average length of nuchal translucency

Back 13

1 mm

Front 14

Nuchal translucency as part of first trimester screening can pick up what condition that can't be ID'd in quad screen?

Back 14

trisomy 13

Front 15

What % of Down cases are picked up by first trimester serum (PAPP-A and hCG) markers alone? NT alone? Combined test?

Back 15

serum=60%
NT=60%
combined=80%+

Front 16

Detection rate of Down by first trimester screen vs. quad screen

Back 16

first=~85%
quad=~76

Front 17

What is the main problem with sequential screening?

Back 17

High false positive rate, because those at highest risk are pulled out after the first trimester screen.

Front 18

Twins that are monochorionic/diamniotic--identical or fraternal?

Back 18

Can be either

Front 19

What type of twins are ALWAYS monozygotic, w.r.t. the amnion and chorion?

Back 19

monochorionic/monoamniotic

Front 20

Mean gestational age for twins? triplets?

Back 20

twins=36.5 weeks
triplets=33 weeks

Front 21

Risks to singleton babies concieved by ART

Back 21

small for gest. age
preterm delivery
pre-eclampsia
gest. diabetes
placenta previa
placental abruption
C-section

Front 22

What % of multiples come from ART?

Back 22

30%

Front 23

Maternal risks assoc. with multiples

Back 23

pre-eclampsia
hemorrhage
pregnancy-induced hypertension
death

Front 24

Risks of first trimester fetal reduction

Back 24

pregnancy loss
infection
IUGR
termination of wrong fetus
leakage
bleeding
psychological issues

Front 25

Risks of second trimester fetal reduction

Back 25

pregnancy loss
mom gets clot
preterm labor
IUGR
infection
risk to other fetuses (bleeding, leakage)
wrong fetus
psychological issues

Front 26

Some AD conditions assoc. with advanced paternal age

Back 26

achondroplasia
NF
Marfan
Treacher Collins
Waardenberg
Thanatophoric dysplasia
OI
Apert

Front 27

Some X-linked conditions assoc. with advanced paternal age

Back 27

Fragile X
Hemophilia A
Hemophilia B
DMD
Incontinentia Pigmenti
Hunter
Retinitis Pigmentosa

Front 28

In what % of CVSs does the karyotype reflect that of the fetus?

Back 28

98-99%

Front 29

How frequent is confined placental mosaicism?

Back 29

1-2% of cases

Front 30

Possible mechanisms for CVS-induced limb reduction defects

Back 30

vascular disruption
release of vasoactive substances
strong contractions
thromboembolism
amniotic bands

Front 31

Independent sequential screening, in which a cutoff of 1:270 is used for each screen, has a detection rate of what? FPR?

Back 31

98% DR
10-20% FPR

Front 32

Sequential screening using what cutoffs has the highest detection with lowest FPR? What are the DR and FPR?

Back 32

1st trimester screen positive >1:60
2nd trimester screen positive >1:190
93% DR
2-4% FPR

Front 33

Describe contingency screening

Back 33

All patients have NT/PAPP-A/hCG
Very high risk (1:60) have CVS
VERY low risk (1:1200) have no further testing
Intermediate risk (1:60-1200) have quad screen
High quads (1:190) have amnio

Front 34

Of the 1st 64 cells of a zygote, how many contribute toward the fetus?

Back 34

4=embryo
12=extraembryonic structures
48=trophectoderm

Front 35

Describe the independent sequential screen.

Back 35

1st trimester combined screen, CVS if positive (>1:270)
2nd trimester quad, don't use previous risk. Positive is > 1:270
High detection (~98%), 10-20% FPR

Front 36

Describe the sequential screen.

Back 36

1st trimester combined screen, CVS if positive (>1:60)
Everyone else waits for result until 2nd trimester.
2nd trimester quad, don't use previous risk. Positive is > 1:190
High detection (~93%), 2-4% FPR

Front 37

Describe integrated screening

Back 37

1st trimester NT + PAPP-A
No result given.
2nd trimester quad screen.
Total risk given.
~88% DT

Front 38

Describe PGD using polar body removal

Back 38

Pipette pierces zona pellucida and enters perivitelline space
First polar body removed
In AR disease, if polar body has 2 affected alleles, egg is unaffected. If heterozygous, must check 2nd polar body too.

Front 39

Disadvantages of polar body removel for PGD

Back 39

maternal info only
no gender info
may require 2 biopsies
miss any post-zygotic errors

Front 40

Indications for PGD for aneuploidy

Back 40

AMA
multiple losses
previous aneuploidy
multiple failed IVFs
aneuploidy in parent

Front 41

Effect of PGD for recurrent pregnancy loss

Back 41

PGD(for aneuploidy) is highly effective at reducing pregnancy loss for couples with multiple previous miscarriages

Front 42

Name some ways to make PGD for single gene disorders more accurate

Back 42

Linkage analysis to prevent allele dropout in PCR
Do ICSI to prevent contamination from other sperm outside the egg
Do prenatal invasive testing to confirm later

Front 43

Criteria for heterozygote screening programs

Back 43

High freq. of carriers in population
Inexpensive, dependable test, low FPR, FNR
Access to counseling for couples
Acceptance and voluntary participation by population

Front 44

Advantages of preconceptional counseling for carrier screening

Back 44

avoid conception
adopt
donor sperm/egg
PGD
prenatal diagnosis

Front 45

What % of those of AJ ancestry carry at least one recessive mutation?

Back 45

1/5-1/7

Front 46

Main problem with carrier screening and people's memory of test results

Back 46

Don't understand that a negative is never definite, as not all mutations can be picked up. Don't seem to remember info months after testing.

Front 47

Freq. of Tay-Sachs among AJs? Carrier freq.?
Hex-A test detects what % of carriers?

Back 47

1/3000
1/30
98%

Front 48

Carrier screening for what conditions is standard of care of AJs?

Back 48

Tay-Sachs
cf
Canavan
Familial dysautonomia

Front 49

Disorders frequent among AJ, which are amenable to screening

Back 49

Tay-Sachs
Canavan
cf
Familial dysautonomia
Fanconi anemia group C
Neimann-Pick A
Mucolipidosis IV
Bloom
Gaucher

Front 50

Tay-Sachs is common in which populations?

Back 50

AJ
French Canadian
Cajun
Irish

Front 51

Why can't Tay-Sachs be treated?

Back 51

enzyme replacement is ineffective due to blood-brain barrier
bone marrow transplant diesn't slow/reverse brain damage

Front 52

General population carrier rate of Tay-Sachs compared to AJs?

Back 52

general=1/300
AJ=1/30

Front 53

Features of Tay-Sachs

Back 53

progressive neurodegeneration, starts at 3-6 months
loss of motor skills, inccreased startle response
seizures, blindness, deafness, incapitation

Front 54

Explain the normal and mutant gene product in Tay-Sachs

Back 54

Hex A, the gene, makes hexosaminidase A protein. Hexosaminidase A normally breaks down GM2 gangliosides in nerve cells. Mutations in Hex A prevent production of hexosaminidase A. Accumulation of GM2 gangliosides is toxic, leading eventually to cell death by bursting.

Front 55

Most common Tay-Sachs mutation

Back 55

1278insTATC (82%)

Front 56

Explain the Hex A pseudodeficiency alleles

Back 56

There are 2 clinically benign alleles that result in altered enzyme tht is active in cells, but NOT in serum. These alleles DO NOT cause Tay-Sachs. But enzyme test will look like person is a carrier, or will fall into the 'inconclusive' range. Occurs across all ethnic groups. 35% of non-Jews who test as heterozygotes are found to have this allele, while 2% of AJs have it. Use mutation analysis to further classify.

Front 57

Enzyme range cutoffs for Hex A testing

Back 57

non-carrier=>62.3
inconclusive=57.4-62.2
carrier=<57.3

Front 58

How is Tay-Sachs diagnosed prenatally?

Back 58

Homozygote fetuses have decreased Hex A in amniotic fluid, amniocytes, and chorionic villus.Can also do mutation analysis.

Front 59

Features of Canavan syndrome

Back 59

Severe, progressive CNS deterioration
DD onset 3-5 months
motor delay
macrocephaly
hypotonia, then spasticity
seizures
optic atrophy
death by teens, usually by age 5

Front 60

What gene is assoc. with Canavan?

Back 60

ASPA

Front 61

When the carrier freq. is not known for a given population, use what freq. for calculations?

Back 61

1/100, in general

Front 62

3 common Canavan mutations, in 98% of AJ and 50% of others?

Back 62

E285A
Y231X
A305E

Front 63

In Cancvan syndrome, a decrease in enzyme causes an increase in what? What is the effect?

Back 63

NAA.
Leads to demyelination in the brain.

Front 64

How is Canavan carrier testing done? prenatal testing?

Back 64

gene testing to detect carriers.
prenatally, can do gene test or measure NAA level in amniotic fluid (note that the enzyme itself in NOT what is measured)

Front 65

Features of familial dysautonomia

Back 65

Degeneration of sensory and autonomic neurons
abnormal suck, feeding issues, vomiting, sweating, pain and temperture insensitivity, no tearing

Front 66

Gene assoc. with familial dysautonomia

Back 66

IKBKAP

Front 67

IN 2008, ACMG added which 5 conditions to the standard AJ screen?

Back 67

Mucolipidosis IV
Bloom
Neimann-Pick
Gaucher
Fanconi anemia

Front 68

In 2008, ACMG recommended that who have AJ screening

Back 68

Anyone unsure of heritage who may be AJ
Anyone with at least 1 Jewish grandparent