Genetic Screening And Risk Assessment

Question 1

What three diseases are always screened for in newborns

Answer 1

1. Phenylketonuria
2. Galactosemia
3. Hypothyroidism

Question 2

Phenylketonuria is a ______ inheritance pattern and the gene associated is ______

Answer 2

Autosomal recessive
PAH gene (phenylalanine hydroxylase)

Question 3

Phenylketonuria is defined by

Answer 3

The inability to digest phenylalanine, which with phenylpyruvic acid accumulate in the blood, phenylketonuria appear in the urine

Question 4

Symptoms of untreated phenylketonuria

Answer 4

1. Intellectual disabilities/mental retardation
2. Seizures
3. Tremors
4. Hyperactivity
5. Stunted growth

Question 5

Why is an accumulation of phenylalanine in the blood toxic?

Answer 5

It can saturate large neutral amino acid transporters (LNAAT, LAT-1) located and the blood-brain barrier blocking important amino acids from entering (esp. tyrosine and tryptophan)

Question 6

If phenylketonuria is untreated, irreversible intellectual disabilities occur at _____ age

Answer 6

One month of age

Question 7

Excess phenylalanine leads to decreased tyrosine to the brain which leads to decreased production of

Answer 7

Dopamine and adrenaline

Question 8

Phenylketonuria treatment:

Answer 8

Restriction of dietary phenylalanine (not completely)

Question 9

What is maternal PKU

Answer 9

Mom has PKU, but eats more phenylalanine since brain has developed. Fetus affected by high phenylalanine, even without gene

Question 10

What is PGD

Answer 10

Preimplantation genetic diagnosis

Question 11

PGD (preimplantation genetic diagnosis) mechanism:

Answer 11

After IVF, a single cell is removed from eight-cell blastomere, PCR amplifies DNA, embryos without mutation can be implanted

Question 12

Which prenatal diagnostic tests are invasive?

Answer 12

Amniocentesis, chorionic villus sampling (CVS), cordocentesis, preimplantation genetic diagnosis (PGD)

Question 13

Which pregnancy screenings are non-Invasive?

Answer 13

Nuchal translucency (NT) and maternal serum screening, ultrasound, cell-free fetal DNA

Question 14

Which pregnancy screenings test for chromosomal abnormalities

Answer 14

Amniocentesis, chorionic villus sampling (CVS), nuchal translucency (NT) and maternal serum screening, cell-free fetal DNA

Question 15

Which pregnancy screenings have fetal loss risk

Answer 15

Amniocentesis (0.5%), chorionic villus sampling (CVS) (1%)

Question 16

Which pregnancy screenings have no risk associated

Answer 16

Nuchal translucency (NT) and maternal serum screening, ultrasound, cell-free fetal DNA

Question 17

Ultrasound pregnancy screening tests for

Answer 17

Structural abnormalities like neural tube defects or congenital malformations

Question 18

Gestational age =

Answer 18

The number of weeks inside the start of the last me trial period (adds roughly 2 weeks to age of fetus)

Question 19

Optimal time for amniocentesis

Answer 19

15-20 weeks

Question 20

Amniocentesis tests for

Answer 20

Cytogenetic analysis, DNA based testing, fetal a-fetoprotein (AFP)

Question 21

High AFP levels indicate significant risk for

Answer 21

Neural tube disorders

Question 22

Low AFP levels indicated significant risk of

Answer 22

Trisomies (Down Syndrome)

Question 23

Chorionic Villus Sampling (CVS) optimal time

Answer 23

10-12 weeks

Question 24

Chorionic villus sampling (CVS) sample collected

Answer 24

Fetal trophoblastic tissue (no AFP!!)

Question 25

Chorionic Villus Sampling tests for

Answer 25

Cytogenetic analysis, DNA based testing

Question 26

Ultrasound Optimal time

Answer 26

16-18 weeks

Question 27

Maternal Serum screening and Nuchal Translucency (NT) optimal time

Answer 27

11-14 weeks

Question 28

Maternal Serum screening and Nuchal Translucency (NT) sample collected

Answer 28

Maternal serum + ultra sound

Question 29

Increased nuchal translucency suggests:

Answer 29

A higher risk of chromosomal anomalies or congenital heart disease

Question 30

What makes determining high AFP levels difficult in maternal serum screening

Answer 30

Substantial overlap in maternal AFP levels between normal and Down syndrome pregnancies

Question 31

Which pregnancy screening method is beginning to replace standard maternal AFP

Answer 31

Triple screen

Question 32

Triple screen tests for which proteins

Answer 32

1. Maternal serum (AFP) 2. Human chorionic gonadotropin (hCG) (produced within placenta) 3. Estriol (produced by fetus + placenta)

Question 33

Triple screen testing optimal time

Answer 33

16-18 weeks

Question 34

Triple screen drawbacks

Answer 34

Requires information about fetal number (twins, etc), many concerns with false positives

Question 35

In 95-98% of anencephaly, MSAFP= hCG= Estriol=

Answer 35

MSAFP = increased | All else normal

Question 36

In 85-90% of spina bifida, MSAFP= HCG= Estriol=

Answer 36

MSAFP increased | All else normal

Question 37

In 60-65% of Down syndrome, MSAFP = HCG= Estriol =

Answer 37

``` MSAFP = decreased HCG= increased Estriol = decreased ```

Question 38

What does cell-free fetal DNA use for pre-natal screening

Answer 38

Cell-free fetal DNA that is shed into themother’s blood during pregnancy

Question 39

Can cell-free fetal DNA testing be used for all pregnancies?

Answer 39

Not for use in pregnancies with multiples

Question 40

Cell-free fetal DNA testing optimal time

Answer 40

Can be performed anytime after 10 weeks

Question 41

Which pregnancy screening method is offered to women over 35 (and not younger women due to high cost)

Answer 41

Cell-free fetal DNA

Question 42

What can cell-free fetal DNA testing detect?

Answer 42

Trisomies, aberrant numbers of sex chromosomes, sex of the baby