Genetic Screening

Question 1

What is involved in a prenatal genetic history (both genetic parents):

Answer 1

Health hx
OB hx
Genetic hx
Occupational/Environmental hx
Ethnic origin
First degree relatives
Teratogen exposure
Gestational parent age >35
Partner/donor age >50

Question 2

What genetic diseases are routinely tested for in prenatal screening?

Answer 2

Trisomy 13 (Patau Syndrome)
Trisomy 18 (Edward’s Syndrome)
Trisomy 21 (Down’s Syndrome)

Question 3

Types of Open Neural Tube Defects (ONTD):

Answer 3

Spina Bifida
Ancephaly
Encephalocele

Question 4

How do ONTD occur?

Answer 4

associated w/ folic acid deficiency
results in neural tube does not form & close properly

Question 5

Degrees of Spina bifida:

Answer 5

-spina bifida occulta (gap created in spine d/t incomplete fusion; sac of fluid absent)
-meningocele (gap created in spine; sac of CSF present)
-myelomeninocele (gap created in spine; sac of CSF and buldging spinal cord –> causing partial or complete paralysis & hydrocephalus

Question 6

Define anencephaly and encephalocele:

Answer 6

-anencephaly: abnormal or absent brain matter
-encephalocele: sac containing brain/meninges/CSF forms outside of skull d/t bone defect

Question 7

Prenatal screening vs diagnostics:

Answer 7

-screening: assess level of risk
ex: U/S, blood draws (no parental/fetal risk
-diagnostic: definitive answer if disorder present
ex: anmiocentesis, chorionic villi sampling

Question 8

What is aneuploidy

Answer 8

abnormal number of chromosomes

Question 9

Types of screening for aneuploidy & ONTD:

Answer 9

-First Trimester Screen (FTS)
-Second trimester maternal serum screening
-Sequential and Integrated Screening
-Non-invasive Prenatal Testing (NIPT)
-Second trimester U/S (20 wk anatomy scan)

Question 10

What does First Trimester Screen involve?

Answer 10

-performed at 10-14 wks
-involved fetal U/S and maternal blood samples
-screens for trisomy 13, 15, 18 & 21
-maternal sample: HCG and PAPP-A (pregnancy associated plasma protein A)
-high level of HCG associated w/ down’s snydrome
-low level of PAPP-A associated w/ down’s syndrome
-fetal U/S: nuchal translucency u/s and dating/viability

Question 11

Nuchal translucency (NT) measurement of ___ indicates risk of aneuploidy

Answer 11

> 3mm

Question 12

Second trimester maternal serum screening

Answer 12

-performed at 15-22 wks
-involved maternal blood samples
-screens for trisomy 13, 18, 21 & ONTD
-Quadruple Marker Screen (AFP, uE3, hCG and inhibin-A)

Question 13

What are the 4 biomarkers in Quadruple Marker Screen:

Answer 13

-AFP (Alpha Fetoprotein): assess risk of ONTD
-hCG (Human chorionic gonadotropin): assess risk for down’s
-uE3 (estriol): lower levels in baby w/ down’s
-Inhibin A: assess risk for down’s

Question 14

Second trimester fetal U/S

Answer 14

-performed at 18-22 wks
detailed anatomy scan
-assess for soft markers for aneuploidy and ONTD
-Very accurate for ONTD
-Least accurate for Down’s (21)
-Abnormal scan –> counseling –> diagnostics (amniocentesis)

Question 15

Non-invasive prenatal testing (NIPT):
includes:

Answer 15

-parental blood test
-recommended at 9-10 weeks
-uses cell free DNA (cfDNA) of both parent & fetus
-screen for: sex chromosome aneuploidy & trisomy 13, 18 & 21
can detect fetal sex
-abnormal scan –> counseling –> amnio or CVS

Question 16

Sex aneuploidy examples:

Answer 16

-Turner’s (X)
-Klinefelter (XXY)
-Triple X or Trisomy X (XXX)
-XYY syndrome

Question 17

Drawbacks of NIPT

Answer 17

-data obtained from corporate sponsored biomed research
-lack of regulation
-unable to detect mosaicism –> genetic conditions effects some cells but not all

Question 18

Diagostic Invasive Prenatal testing:

Answer 18

-chorionic villus sampling (CVS)–> 9-14 wks
–higher miscarriage risk
–obtained transcervically or transabdominally
–collects chorionic villi from placenta (contained fetal DNA)
-amniocentesis –> 14-16 wks
–obtained transabdominally
–collects anmiotic fluid
cordocentesis
–direct fetal blood sample
–detects chromosomal mosaicism

Question 19

Carrier Screening

Answer 19

-Everyone –> CF
-Africans, Blacks, Asian, Middle Eastern –> hemoglobinopathies (sickle cell & thalassemias)
-Ashkenazi jew –> CF, tay sachs, familial dysautonomia
-Northern Euros –> CF and spinal muscular atrophy (SMA)