Exam 4 - PGT (cont.) and Birth Defects

Question 1

What can be determined from PGS (PGT-A) and PGD (PGT-M)?

Answer 1

PGS/PGT-A : number of chromosomes, aneuploidy, sex, mosaicism, etc.
PGD/PGT-M: specific gene mutations/single gene disorders

Question 2

What are arguments in favor of universal PGT-A?

Answer 2

decreased termination due to aneuploidy
increased pregnancy rates
reduced miscarriage rates

Question 3

What is aCGH?

Answer 3

array comparative genomic hybridization

Question 4

Why does PGT-A increase ongoing pregnancy rates and decrease pregnancy loss rate?

Answer 4

embryos with aCGH testing prior to transfer means only euploid embryos get transferred

Question 5

What are some considerations for PGT?

Answer 5

genetic counseling must include alternate strategies (such as donor gametes or adoption)
diagnostic methodology may be expensive
biopsy may damage embryo
not all genetic abnormalities can be diagnosed
there may be no “unaffected” embryos to transfer
controversial applications (gender selection, savior siblings, designer babies)
misdiagnosis may result from mosaicism
prenatal diagnosis is recommended for confirmation of PGS/PGD

Question 6

What is a birth defect?

Answer 6

abnormality of structure, function, or metabolism that is present at birth and results in a physical or mental disability/death

Question 7

What is a congenital defect?

Answer 7

any physical anomaly which is recognizable at birth

Question 8

How common are birth defects?

Answer 8

about 120,000 babies (1 in 33) in the US are born with birth defects each year

leading cause of death in the first year of life

Question 9

What are the three causes of birth defects?

Answer 9

chromosomal defects, single gene defects, and environmental factors

Question 10

What are chromosomal birth defects?

Answer 10

too many or too few chromosomes (aneuploidy) such as trisomy 21, 13, and 18

Question 11

What are single gene defects?

Answer 11

mutation in a gene (or multiple genes) causes a disorder
ex:
achondroplasia, cystic fibrosis, hemophilia

Question 12

What are environmental factor birth defects?

Answer 12

teratogens (environmental substances that cause birth defects)
ex:
alcohol (cause fetal alcohol syndrome)
drugs/medication (cocaine, acne medication isotretinoin)
infections (STDs)

Question 13

How can birth defect risk be reduced?

Answer 13

consult a genetic counselor if birth defects are present in family history, avoid smoking/alcohol/drugs, STD screening, multivitamin with folic acid

Question 14

What is the recommended folic acid dose?

Answer 14

400 micrograms to 4 mg

Question 15

When does neural tube formation occur? Why is this important?

Answer 15

15-28 days of development (from fertilization)
often before women know they are pregnant so defects can be attributed to environmental (or genetic) factors

Question 16

What are the two neural tube defects we discussed? How do they happen?

Answer 16

anencephaly:
- upper part of neural tube does not close all the way
- baby is born with parts of brain and skull missing

spina bifida:
- can happen anywhere along the spine where lower part of the neural tube doesn’t close all the way
- causes physical and mental disability that range from mild to severe

Question 17

Failure of the neural plate to fuse in what regions cause anencephaly and spina bifida?

Answer 17

anencephaly: failure to close in region 2

spina bifida: failure to close in region 5

Question 18

What processes are folic acid important for?

Answer 18

DNA synthesis, DNA repair, DNA methylation, cofactor in biological reactions, rapid cell division and growth, preventing major birth defects in brain and spine such as anencephaly and spina bifida

Question 19

How much does folic acid decrease risk of neural tube defects?

Answer 19

decrease risk by 50-70%

Question 20

How has the government tried to increase women’s intake of folic acid?

Answer 20

1992, US Public Health Service recommended women of childbearing age increase consumption of folic acid to reduce spina bifida and anencephalus

1996, FDA authorized that all enriched cereal grain products be fortified with folic acid

Question 21

What ways can birth defects be diagnosed before birth?

Answer 21

blood tests, ultrasound, chorionic villus sampling, amniocentesis

Question 22

How can blood tests be used to test for birth defects?

Answer 22

Non Invasive Prenatal Testing (NIPT) done as early as 7 weeks from LMP

uses cell free fetal DNA:
- primary source in maternal circulation though to be apoptosis of placental cells (syncytiotrophoblasts)
- most reliably used for sex determination and sex linked disorders, potential for gender discrimination
- most commonly used to diagnose trisomy 13, 18, and 21 and single gene defects of paternal origin

Question 23

How is ultrasound used in each trimester?

Answer 23

first trimester: establish dates of pregnancy, detect heartbeat by 7 weeks from LMP, fetal movement at 7-8 weeks, number of fetuses, ectopic pregnancy or miscarriage

second trimester: fetal anatomy for presence of abnormalities, discover sex of fetus around 14 weeks

third trimester: monitor fetal growth, check amount of amniotic fluid, determine position of fetus and placenta

Question 24

What is CVS?

Answer 24

chorionic villus sampling

• performed between 10-12 weeks from LMP (when placenta is fully functional)
• sample of placental tissue taken under ultrasound guidance (contains same genetic info as fetus and can be tested for chromosomal abnormalities and some other genetic defects)
• does not provide info on neural tube defects

Question 25

What type of procedure is used for CVS?

Answer 25

transcervical or transabdominal, depending on the position of the fetus in the uterus

Question 26

What is amniocentesis?

Answer 26

performed between 15-20 weeks from LMP (when the volume of amniotic fluid is max relative to size of fetus)

sample of fluid that surrounds the fetus taken under ultrasound guidance, contains cells shed by the fetus and alpha fetoprotein (indicates neural tube defect)

provides info about neural tube defects, chromosomal abnormalities, and some other genetic defects

Question 27

Chromosomal abnormalities cannot be detected by which method of testing?

Answer 27

ultrasound

Question 28

Cells in the amniotic fluid are identical to cells of…

Answer 28

the fetus

Question 29

Describe the risk/benefit ratio for CVS and amniocentesis

Answer 29

Starting at age 35, the risk of CVS or amniocentesis causing miscarriage is lower than the risk of having a baby with down syndrome

Before 35, the risk of miscarriage is greater than the risk of having a baby with down syndrome

Question 30

What are arguments in favor of prenatal screening?

Answer 30

pursue interventions, plan for child with special needs, address anticipated lifestyle changes, identify support groups and resources, make decisions about carrying child to term

Question 31

What are arguments against prenatal screening?

Answer 31

parents should accept results regardless of outcome, making decisions about carrying a child to term is not an option because of personal/moral/religious reasons, testing may pose risk of harming the developing baby

Question 32

How are birth defects diagnosed after birth?

Answer 32

newborn screening tests
- every state screens newborns before they leave the hospital for certain genetic, metabolic,
hormonal and functional disorders
- most birth defects have no immediate visible
effects on a baby but, unless detected and treated early, can cause physical problems, mental
retardation and, in some cases, death
- except for hearing screening, all newborn
screening tests are done using a few drops of blood
from newborn’s heel

Question 33

How many disorders does the state of Arizona screen for in newborn screening? What are the categories of disorders?

Answer 33

31
endocrine, amino acid, fatty acid oxidation, organic acid, hemoglobin, other disorders
hearing loss, critical congenital heart defects

Question 34

What is PKU? How is it treated?

Answer 34

phenylketouria

• babies cant process phenylalanine (amino acid in most food)
• affects 1/25,000 babies
• without treatment, it builds up in bloodstream and causes brain damage and mental retardation
• treatment is a low-phenylalanine diet that is generally followed throughout life