Fetal Genetic Abnormalities Flashcards
Screening vs. Diagnostic testing
- Screening: determining if the fetus is at high risk or low risk to have a particular condition
- Diagnosis: determining if the fetus is affected or unaffected
Types of screening tests
- Response to a question
- Blood test
- Ultrasound
Types of diagnostic tests
- Chorionic villus sampling (CVS)
- conducted 11-13wks (allows for earlier answers)
- Amniocentesis
- conducted anytime after 15wks
- Ultrasound
- can be both a screening and diagnostic test
Diseases screened for
- CF
- Common chromosome abnormalities
- trisomy 21, 18, 13
- XXY
- XXX
- XYY
- 45, X (Turner syndrome)
- Open neural tube defects
- Ventral wall defects
- Cystic hygroma
- Holoprosencephaly
- Arthrogryposis
Cystic Fibrosis
- CF is the most common serious autosomal recessive disorder in caucasians
- CF occurs in approx. 1:2,500 live caucasian births in the U.S.
- Median survival of a CF pt is approx. 31yrs
- 1 in 31 Americans (more than 10 million) are carriers
- The carrier freq. and incidence varies among ethnic groups
- CF is the result of a basic defect in the (CFTR) gene
- Cystic fibrosis has variable presentations (some kids better than others)
CF Prenatal carrier testing
- Can be offered up to 20wks
- A neg. screening test does not eliminate the possibility that an individual is a carrier of the CF gene
2 Chromosome abnormalities not assoc. w/ advanced maternal age
- Turner’s syndrome
- considered a random mutation
- XYY
- mother cannot contribute Y chromosome
Newborn with down syndrome presentation
- Aside from facial features 80% of these infants will have extra skin on the back of their neck (best diagnostic clue on physical exam)
Nuchal Translucency
- Screening test conducted in first trimester b/w 11-14wks and measure the fluid space in the back of the neck; anything under 3.5mm is normal (but depends on gestational age) anything over (>4mm) is an indication for an increased risk of fetal abnormalities
- 10% of fetuses w/ NT of 3mm have major abnormalitites
- 90% of fetuses w/ NT of 6mm have major abnormalities
Sequential Screen: 2 steps preliminary and final
First trimester (11-14wks) preliminary measurements are taken:
- Maternal age
- Nuchal translucency
- Human chorionic gonadotropin (increased in down syndrome)
- Pregnancy assoc. plasma protein A (decreased in down syndrome)
If the preliminary tests suggest the mothers risk of a down syndrome baby is >1/50 (high risk) then we offer her a diagnostic test. If the risk is <1/50 the mother goes on for a 2nd portion of testing…
Second trimester (15-22wks)
- Alpha feto-protein (low in downs)
- Estriol (low in downs)
- hCG (high in downs)
- Inhibin-A (low in downs)
If the risk comes back now >1/250 we call them high risk and offer them a diagnostic test. This process picks up 90% of fetuses w/ down syndrome
Circulating cell-free fetal (ccff) DNA
- Noninvasive prenatal testing (NIPT)
- Maternal blood draw that takes analyzes the little fragments of fetal DNA floating in the blood stream
- The source of ccff DNA is thought to be from placental and fetal-derived cells
- Recent studies indicate 5-20% of DNA in maternal blood is actually fetal in origin
- DNA analysis does not differentiate which fragments come from the mother and which from the fetus; implement quantitative analysis comparing to expected amts
- Very low false-pos. rate
Chromosome Dosage Analysis for Trisomy 21 (Interpreting the data from ccff)
- Measure the small DNA fragments derived from chromosome 21 in maternal blood
- This measurement includes both maternal and fetal chromosome 21 fragments
- If the amt exceeds a critical threshold relative to expected amts from normal reference samples, it indicates an excess number of chromosome 21’s (i.e. trisomy 21)
- Turn around time (currently) approx. 7 days
5 indications for offering ccff testing
- Advanced maternal age
- Ultrasound abnormality
- Someone who had an abnormal sequential screening and doesn’t want amnio or CVS
- Family history of chromosomal problem
- If 1 parent has a Robertsonian translocation; chromosome 21 fragment is stuck on another chromosome
Sequential vs NIPT
Sequential
- 2 blood tests and an US
- 11-14wks and 15-20wks
- FPR 4%
- Det’n rate 90%
- Tri 18 and 21
- Screens for NTD’s
- Contraindication: bleeding
- Donor egg: yes
- Vanishing twins: no
- Twins: yes
NIPT
- 1 blood test
- Anytime after 10wks
- FPR 0.1% (40x better)
- Det’n rate 99%
- Tri 13, 18 and 21, sex chromosomes 45, X , XXY, XXX, XYY, triploidy, microdeletions
- Does not screen for NTD’s
- Can be done if bleeding
- Donor egg: yes, most labs
- Vanishing twins: no
- Twins: most labs
Open neural tube defects
- Anencephaly
- absence of a skull (top doesn’t close)
- Myelomeningoecele
- opening in the lower spine (bottom doesn’t close)
- Encephalocele
- skin defect in the back of the occipital skull
