Prenatal Screening Flashcards
Positive predictive value
% patients with positive screen that are affected
Negative predictive value
% patients with negative screen that are not affected
Likelihood ratio
Will tell you how to adjust pretest odds to get posttest odds
For an autosomal recessive disease, the sibling of an affected patient has a ___ chance of being a carrier
2/3
Given that dad has 2/3 chance of being a carrier, mom has 1/12 chance, what is the risk for affected child?
(1/2) x (1/12) x (1/2) x (2/3)
Cystic fibrosis
Autosomal recessive
CFTR gene
Chloride channel
Commonly deltaF508/ G542x but 1000+ known mutations
Symptoms: lung, cor pulmonale, pancreatic insufficiency, infertility
1/29 caucasians are carriers
Screen parents, then with CVS/amnio if both parents carriers (1/4 risk)
Sickle cell
Autosomal recessive Vaso-occlusive crises Hemolytic anemia Screen mom with hemoglobin electrophoresis, then dad if patient carries HBs Carrier freq: 1/12 in AA
Tay-Sachs
Autosomal recessive
Hexosamindase A deficiency > GM2 gangliosides build up
Gray matter lysosomal storage disease
Carrier freq: 1/27 in Ashkenazi Jews, eastern Euros
3-10 months after birth: hyperacusis, loss of alertness, myoclonic/akenitic seizures, cherry red spot in macula
Thalassemias
hemolytic anemia, RBC destroyed in bone marrow, liver, spleen
Beta-thalassemia
AR
Mediterraneans, asians, africans
Too few beta chains > usually presents postnatally (when beta normally replaces gamma)
Screen with CBC (mild hemolytic anemia with low MCV), then get Hgb electrophoresis (shows more alpha than beta > Hgb A2)
Alpha-thalaseemia
AR
Too few alpha chains
4 alpha genes, 2/4 mutations can be cis (asians) or trans (africans)
If both parents have cis mutations = 25% infants will get severe form; trans = usually will become carrier
4 genes: fetal hydrops- incompatible with life, splenomegaly, Hb electro shows no HbF, no HbA, lot of Hb Bart’s (4 gammas)
3 genes: HbH disease - beta chains build up, oxidative damage, destruction, Hb electro shows Hb Barts and HbH (beta tetramers), Barts goes away as gamma chains replaced
2 genes: trait, mild phenotype, microcystic anemia
SCREEN WITH CBC, THEN HB ELECTROPHORESIS!
Chromosomal abnormalities
Trisomy 21 Trisomy 18 Trisomy 13 NTD Turner Syndrome Klinefelter syndrome
QUAD SCREEN
- verify dates and rule out multiple gestations
- MSAFP: low in 21, 18; high in NTD
- Estriol: low in 21, 18
- BhCG: high in 21, low in 18
- Inhibin-1: High in 21, normal in 18
* levels in 13 depend on defects
Down Syndrome
Flattened nasal bridge, small size, cup-shaped ear, sandal-gap toes, hypotonia, simian crease, epicanthic fold, oblique palpebral fissues, protruding tongue, short broad hands
Higher rates of stillbirth, miscarriage
IQ 40-90
A/W duodenal atresia, cardiac defects, short limbs, nasal bone hypoplasia
Trisomy 18, Edwards
Clenched fists, overlapping digits, rocker bottom feet, VSD, tetFal, omphalocele, CD hernia, NTD, choroid plexus cysts, fetal/neonatal death
Trisomy 13, Patau
holoProsencephaly, cleft lip and palate, cystic hygroma, single nostril, omphalocele, hypoplastic left heart, clubfoot.hand, polydactyly, overlapping fingers
Turner syndrome
XO
Wide spaced nipples, shield like chest, lymphedema, primary amenorrhea, coarctation of aorta, short 4th metacarpal, receding hairline
Klinefelter syndrome
47, XXY
Small, firm testes, hyalinized seminiferous tubules, infertility, gynecomastia, mental retardation, elevated gonadotropin levels
Congenital anomalies
Organogenesis Radiation Neural tube defects Cardiac defects Potter sequence Fetal anemia
Organogenesis
Weeks 3-8 after conception (wks 5-10 EGA)
Insult before = probably will lose pregnancy
Radiation
Radiation during weeks 8-15 has greatest risk of fetal microcephaly / severe MR
Neural tube defects
Defective closure by 4 wks after conception (6 wks EGA). Need folic acid before!
Spina bifida, anencephaly, etc. Elevated AFP
Spina bifida: see lemon sign (concave frontal bones), banana sign (curved cerebellum) on U/S.
Cardiac defects
Follow with fetal echo, consult peds cards Week 3 (wk 5 EGA) is key time
VSD: failure of ventricular walls to form
TetFal: overriding aorta, pulmonary stenosis, RV hypertrophy, VSD
Transposition of the great arteries (PA/ Ao into wrong vent)
Coarctation of the aorta: generally preductal if congenital
PDA → Eisenmenger syndrome
Hypoplastic left heart: worst outcome with surgery
Potter sequence
Renal failure → anhydramnios → pulmonary hypoplasia / contractures
From bilateral renal agenesis, but also if posterior urethral valves / extrophy with obstruction / etc.
Embryology:
Pronephros → degenerates
Mesonephros (Wolffian duct) → gives off [ureteric bud → urinary collecting system (tubules, calyces, renal pelvis, ureter)], then degenerates in females, turns into vas /epidydimis / ejaculatory duct / seminal vesicles if T around in guys.
Metanephros → kidney
Paramesonephric duct (Mullerian) → Fallopian tubes, uterus, cervix, upper 1/3 of vagina
Fetal anemia
If Rh isoimmunization, hydrops, other concerns for anemia, get PUBS (can get Hct /transfuse too if needed!)
PUBS= Percutaneous umbilical cord blood sampling
