Prenatal Iii

Front 1

3 places where AFP is synthesized

Back 1

yolk sac
fetal GI tract
fetal liver

Front 2

Name 3 factors that affect maternal sesrum AFP

Back 2

1. maternal weight
2. maternal race
3. insulin dependent diabetes mellitus

Front 3

MSAFP testing=normal.
What next?

Back 3

nothing

Front 4

MSAFP testing=>2.0 MoM
What next?

Back 4

Repeat test.

Front 5

MSAFP testing=>2.0 MoM
Repeat test=normal
What next?

Back 5

nothing

Front 6

MSAFP testing=>2.0 MoM
Repeat test=>2.0 MoM
What next?

Back 6

dating utrasound

Front 7

MSAFP testing=>2.0 MoM
Repeat test=>2.0 MoM
Dating ultrasound=as expected
What next?

Back 7

Counseling, targeted ultrasound, decide on amnio

Front 8

MSAFP testing=>3.0 MoM
What next?

Back 8

Dating ultrasound

Front 9

4 possible explanations for high MSAFP

Back 9

wrong dates
twins
fetal demise
anomaly

Front 10

When shoud blood be drawn for the quad screen?

Back 10

15-18 weeks

Front 11

Quad screen positive.
What next?

Back 11

confirm gestational age

Front 12

Quad screen positive.
Gestational age confirmed.
What next?

Back 12

Counsel, offer amnio

Front 13

Quad screen positive.
Gestational age found to be too early.
What next?

Back 13

Redraw at 15-18 weeks.

Front 14

Quad screen positive.
Gestational age found to be later than thought.
What next?

Back 14

Recalculate risk based on new age.

Front 15

True or false. An abnormal quad result for Down screening should never be repeated.

Back 15

True.

Front 16

Cutoffs for quad screen for tri 18 per analyte

Back 16

AFP </= 0.75 MoM
estriol </= 0.60 MoM
hCG </= 0.55 MoM

Front 17

Risk of a 30 year old for tri 18?
35?
40?

Back 17

30= 1 in 2724
35= 1 in 1152
40= 1 in 338

Front 18

Which is a more effective way to detect tri 18..use cutoffs for each anlyte in quad, or calculate total risk as a whole?

Back 18

Better to calculate full risk (1:100) than to look at each analyte individually. Picks up 80% rather than 60% of tri 18.

Front 19

Multiple marker screening detects what % of Down? tri 18? spina bifida? anencephaly?

Back 19

Down= 80%
tri 18= 80%
spina bifida= 80%anencephaly= >90%

Front 20

Most prevalent lysosomal storage disease

Back 20

Gaucher

Front 21

Most common non-neuronopathic Gaucher mutation. What % have this?

Back 21

N370S
75%

Front 22

Genzyme offers an AJ panel with how many disorders? What are they?

Back 22

11
Usual 9 plus Glycogen storage disease, MSUD

Front 23

Quest offers an AJ panel with how many disorders? What are they?

Back 23

8
The usual ones minus Mucolipidosis IV

Front 24

AJ conditions sometimes included on panels--rarely

Back 24

Usher 1/3
Connexin 26
Familial hyperinsulinism
Lipoamide dehydrogenase deficiency
Nemaline myopathy

Front 25

Location of alpha and beta hemoglobin genes

Back 25

alpha globin gene cluster=chromosome 16
beta globin gene =chromosome 11

Front 26

Describe the predominance of hemoglobin types over time, starting early in gestation.

Back 26

By 6 weeks gestation, fetus has 50% alpha, 50% gamma. These combine to make fetal hemoglobin. By about 12 weeks after birth, gamma is replaced by beta, making normal hemoglobin A. A small amount of fetal persists (1%), and a small amount of delta also persists to make Hemoglobin A2 (3%)

Front 27

Three normal hemoglobins, their constituents, and their percentages

Back 27

Hb A=a2B2 (96%)
Hb A2= a2d2 (3%)
Hb F= a2g2 (1%)

Front 28

What is a thalassemia?

Back 28

A defect in the quantity of hemoglobin due to decreased synthesis of one or more chains

Front 29

Name three ways that hemoglobinopathies occur

Back 29

1. quantitative-decreased synthesis of one or more globin chains
2. qualitative-structural change alters peptide (e.g., hemolytic anemia, altered oxygen transport)
3. hereditary persistence of fetal hemoglobin-no switch from gamma to beta at birth

Front 30

Standard of care for diagnosing sickle cell and other hemoglobinopathies

Back 30

Hemoglobin electrophoresis

Front 31

Consequences of RBC sickling

Back 31

Sickle cells are destroyed, leading to anemia, weakness, impaired mental function.
Proliferation of bone marrow leads to towering of skull.
Clumping of sickle cells causes damage to heart, kidneys, liver, spleen, muscles, joints, brain, all of which cause increased mortality.

Front 32

Most common conditions for which French Canadians/Cajuns are carriers? Frequencies?

Back 32

Tay-Sachs=1 in 30

Front 33

What is hemoglobin C?

Back 33

single nucleotide substitution in B chain:
Glu6Lys

Front 34

Phenotype of Hemoglobin S/C heterozygotes

Back 34

Like sickle-cell, but less severe, less common

Front 35

How many hemoglobin variants exist?

Back 35

over 1200 have been identified

Front 36

What happens in thalassemia?

Back 36

Mutation reduces synthesis or stability of alpha or beta globin chain. Ratio of alpha to beta chains determines phenotype. Excess of normal chain causes damage to RBC membrane, destroys them. Leads to microcytic anemia.

Front 37

Thalassemia testing: What is the cutoff for MCV?

Back 37

If less than 80, proceed with further testing.

Front 38

Thalassemia testing: What if the MCV is less than 80?

Back 38

Do serum iron or ferritin testing.
If decreased, iron-deficiency.
If normal, measure hemoglobin A2.If A2 is normal, suggest alpha thal trait-do molecular testing. If A2 is increased (over 3.5%), suggests beta thal trait-do molecular testing

Front 39

How many alpha globin genes does a normal person have? What if there are fewer?

Back 39

normal =4, 2 per allele
If only 3, silent carrier of alpha thal
If only 2, alpha thal trait (small RBCs possible mild anemia)
If only 1, Hemoglobin H disease
If zero, Barts disease/fetal hydrops syndrome

Front 40

Describe alpha thal carriers in Asians vs. Africans, with respect to which allele has what

Back 40

Africans tend to 2 identical alpha globin clusters--one gene one and one off (mutations in trans). Total alpha production = 2 out of 4 chains. In Asians, they tend to have one allele with both on and one with both off (mutations in cis).

Front 41

What does ACOG say about thalassemia testing?

Back 41

Individuals of African, Southeast ASsian, and Mediterranean descent are at increased risk for being carriers. Offer screening. Uses CBC and hemoglobin electrophoresis. Offer prenatal diagnosis to carrier couples.

Front 42

Standard of care for cf screening

Back 42

Offer 23 mutation panel

Front 43

Frequency of cf in Whites? AJs? Native Americans?

Back 43

whites=1/3300
AJs=1/3900
Native American=1/1500

Front 44

What % of Native American cf alleles are deltaF508?
How about whites? AJs?

Back 44

Native American=None
whites=70%
AJ=30%

Front 45

Explain the Poly T tract in cf

Back 45

A string of thymidine bases in intorn 8 of CFTR gene
Depending on size, can be associated with disorders
Can be 5T, 7T, 9T
7T and 9T are polymorphisms
5T has variable penetrance, and may mess up intron 8 splicing

Front 46

Most common form of inherited MR

Back 46

Fragile X

Front 47

Reasons why it might be worthwhile to screen for Fragile X in pregnancy

Back 47

Will diagnose much earlier, rather than waiting until kid is older and mom is pregnant again
Cost effetive vs. lifetime cost of a child with MR

Front 48

Top two most common AR diseases

Back 48

cf
SMA

Front 49

Detection rate of Genzyme's SMA test

Back 49

94%

Front 50

Pitfalls of prenatal screening

Back 50

non-paternity
identification of fetus' carrier status
informed consent
privacy and discrimination

Front 51

4 risks associated with amnio before 14 weeks

Back 51

Club feet
Miscarriage
Stillbirth
Fluid leakage

Front 52

Can FISH be used to detect a paracentric inversion? Pericentric?

Back 52

Paracentric--no
Pericentric--yes