Genetic Screening And Risk Assessment Flashcards
What three diseases are always screened for in newborns
- Phenylketonuria
- Galactosemia
- Hypothyroidism
Phenylketonuria is a ______ inheritance pattern and the gene associated is ______
Autosomal recessive PAH gene (phenylalanine hydroxylase)
Phenylketonuria is defined by
The inability to digest phenylalanine, which with phenylpyruvic acid accumulate in the blood, phenylketonuria appear in the urine
Symptoms of untreated phenylketonuria
- Intellectual disabilities/mental retardation
- Seizures
- Tremors
- Hyperactivity
- Stunted growth
Why is an accumulation of phenylalanine in the blood toxic?
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)
If phenylketonuria is untreated, irreversible intellectual disabilities occur at _____ age
One month of age
Excess phenylalanine leads to decreased tyrosine to the brain which leads to decreased production of
Dopamine and adrenaline
Phenylketonuria treatment:
Restriction of dietary phenylalanine (not completely)
What is maternal PKU
Mom has PKU, but eats more phenylalanine since brain has developed. Fetus affected by high phenylalanine, even without gene
What is PGD
Preimplantation genetic diagnosis
PGD (preimplantation genetic diagnosis) mechanism:
After IVF, a single cell is removed from eight-cell blastomere, PCR amplifies DNA, embryos without mutation can be implanted
Which prenatal diagnostic tests are invasive?
Amniocentesis, chorionic villus sampling (CVS), cordocentesis, preimplantation genetic diagnosis (PGD)
Which pregnancy screenings are non-Invasive?
Nuchal translucency (NT) and maternal serum screening, ultrasound, cell-free fetal DNA
Which pregnancy screenings test for chromosomal abnormalities
Amniocentesis, chorionic villus sampling (CVS), nuchal translucency (NT) and maternal serum screening, cell-free fetal DNA
Which pregnancy screenings have fetal loss risk
Amniocentesis (0.5%), chorionic villus sampling (CVS) (1%)
Which pregnancy screenings have no risk associated
Nuchal translucency (NT) and maternal serum screening, ultrasound, cell-free fetal DNA
Ultrasound pregnancy screening tests for
Structural abnormalities like neural tube defects or congenital malformations
Gestational age =
The number of weeks inside the start of the last me trial period (adds roughly 2 weeks to age of fetus)
Optimal time for amniocentesis
15-20 weeks
Amniocentesis tests for
Cytogenetic analysis, DNA based testing, fetal a-fetoprotein (AFP)
High AFP levels indicate significant risk for
Neural tube disorders
Low AFP levels indicated significant risk of
Trisomies (Down Syndrome)
Chorionic Villus Sampling (CVS) optimal time
10-12 weeks
Chorionic villus sampling (CVS) sample collected
Fetal trophoblastic tissue (no AFP!!)
Chorionic Villus Sampling tests for
Cytogenetic analysis, DNA based testing
Ultrasound Optimal time
16-18 weeks
Maternal Serum screening and Nuchal Translucency (NT) optimal time
11-14 weeks
Maternal Serum screening and Nuchal Translucency (NT) sample collected
Maternal serum + ultra sound
Increased nuchal translucency suggests:
A higher risk of chromosomal anomalies or congenital heart disease
What makes determining high AFP levels difficult in maternal serum screening
Substantial overlap in maternal AFP levels between normal and Down syndrome pregnancies
Which pregnancy screening method is beginning to replace standard maternal AFP
Triple screen
Triple screen tests for which proteins
- Maternal serum (AFP)
- Human chorionic gonadotropin (hCG) (produced within placenta)
- Estriol (produced by fetus + placenta)
Triple screen testing optimal time
16-18 weeks
Triple screen drawbacks
Requires information about fetal number (twins, etc), many concerns with false positives
In 95-98% of anencephaly,
MSAFP=
hCG=
Estriol=
MSAFP = increased
All else normal
In 85-90% of spina bifida, MSAFP=
HCG=
Estriol=
MSAFP increased
All else normal
In 60-65% of Down syndrome, MSAFP =
HCG=
Estriol =
MSAFP = decreased HCG= increased Estriol = decreased
What does cell-free fetal DNA use for pre-natal screening
Cell-free fetal DNA that is shed into themother’s blood during pregnancy
Can cell-free fetal DNA testing be used for all pregnancies?
Not for use in pregnancies with multiples
Cell-free fetal DNA testing optimal time
Can be performed anytime after 10 weeks
Which pregnancy screening method is offered to women over 35 (and not younger women due to high cost)
Cell-free fetal DNA
What can cell-free fetal DNA testing detect?
Trisomies, aberrant numbers of sex chromosomes, sex of the baby
