Prenatal Screening

Question 1

Positive predictive value

Answer 1

% patients with positive screen that are affected

Question 2

Negative predictive value

Answer 2

% patients with negative screen that are not affected

Question 3

Likelihood ratio

Answer 3

Will tell you how to adjust pretest odds to get posttest odds

Question 4

For an autosomal recessive disease, the sibling of an affected patient has a ___ chance of being a carrier

Answer 4

2/3

Question 5

Given that dad has 2/3 chance of being a carrier, mom has 1/12 chance, what is the risk for affected child?

Answer 5

(1/2) x (1/12) x (1/2) x (2/3)

Question 6

Cystic fibrosis

Answer 6

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)

Question 7

Sickle cell

Answer 7

Autosomal recessive
Vaso-occlusive crises
Hemolytic anemia
Screen mom with hemoglobin electrophoresis, then dad if patient carries HBs
Carrier freq: 1/12 in AA

Question 8

Tay-Sachs

Answer 8

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

Question 9

Thalassemias

Answer 9

hemolytic anemia, RBC destroyed in bone marrow, liver, spleen

Question 10

Beta-thalassemia

Answer 10

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)

Question 11

Alpha-thalaseemia

Answer 11

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!

Question 12

Chromosomal abnormalities

Answer 12

Trisomy 21
Trisomy 18
Trisomy 13
NTD
Turner Syndrome
Klinefelter syndrome

Question 13

QUAD SCREEN

Answer 13

1. verify dates and rule out multiple gestations
2. MSAFP: low in 21, 18; high in NTD
3. Estriol: low in 21, 18
4. BhCG: high in 21, low in 18
5. Inhibin-1: High in 21, normal in 18
   * levels in 13 depend on defects

Question 14

Down Syndrome

Answer 14

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

Question 15

Trisomy 18, Edwards

Answer 15

Clenched fists, overlapping digits, rocker bottom feet, VSD, tetFal, omphalocele, CD hernia, NTD, choroid plexus cysts, fetal/neonatal death

Question 16

Trisomy 13, Patau

Answer 16

holoProsencephaly, cleft lip and palate, cystic hygroma, single nostril, omphalocele, hypoplastic left heart, clubfoot.hand, polydactyly, overlapping fingers

Question 17

Turner syndrome

Answer 17

XO
Wide spaced nipples, shield like chest, lymphedema, primary amenorrhea, coarctation of aorta, short 4th metacarpal, receding hairline

Question 18

Klinefelter syndrome

Answer 18

47, XXY
Small, firm testes, hyalinized seminiferous tubules, infertility, gynecomastia, mental retardation, elevated gonadotropin levels

Question 19

Congenital anomalies

Answer 19

Organogenesis
Radiation
Neural tube defects
Cardiac defects
Potter sequence 
Fetal anemia

Question 20

Organogenesis

Answer 20

Weeks 3-8 after conception (wks 5-10 EGA)

Insult before = probably will lose pregnancy

Question 21

Radiation

Answer 21

Radiation during weeks 8-15 has greatest risk of fetal microcephaly / severe MR

Question 22

Neural tube defects

Answer 22

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.

Question 23

Cardiac defects

Answer 23

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

Question 24

Potter sequence

Answer 24

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

Question 25

Fetal anemia

Answer 25

If Rh isoimmunization, hydrops, other concerns for anemia, get PUBS (can get Hct /transfuse too if needed!)
PUBS= Percutaneous umbilical cord blood sampling