Prenatal Genetics

Question 1

The overall mosaicism rate in CVS is 1-2% (for levels I,II, and III combined). What percentage of the time is this associated with true fetal mosaicism?

Answer 1

10%

Question 2

If level III mosaicism is reported out on a prenatal sample, what is the likelihood that it represents true mosaicism in the fetus?

Answer 2

80%

Question 3

First Trimester Screening

Answer 3

11w0d-13w6d, screening

Nuchal Translucency measurement + PAPP-A + Free b-hCG

Up to 90% sensitive for T21
Groups T18 and T13 together: 91-96% sensitve

If increased NT, could also be associated with an underlying heart defect, Noonan syndrome, etc

Question 4

Quad Screen

Answer 4

15-21 weeks, screening

AFP + hCG + uE3 + DIA

Up to 80% sensitive for T21
Up to 70% sensitive for T18
Up to 90% sensitive for ONTD
No T13 risk given!

Question 5

Decreased PAPP-A, Increased free b-hCG, Increased NT

Answer 5

FTS: Screen positive for Down syndrome

Question 6

Decreased PAPP-A, Decreased b-hCG, Increased NT

Answer 6

FTS: Screen positive for grouping of T13/T18

Question 7

Decreased AFP, Increased hCG, Decreased uE3, Increased DIA

Answer 7

Quad screen: Screen positive for Down syndrome

Question 8

Decreased AFP, Decreased hCG, Decreased uE3,

Answer 8

Quad screen: Screen positive for T18

Question 9

Elevated AFP

Answer 9

Screen positive for ONTD

Question 10

Midline defects (ex. holoprosencephaly, midline cleft, omphalocele)

Answer 10

Think T13

Question 11

Clubfoot and hydrocephalus and/or fruit in the brain

Answer 11

Think ONTD

Question 12

Cystic hygroma

Answer 12

Think hydrops and Turner syndrome and Down syndrome

Question 13

AV canal/endocardial cushion defect

Answer 13

Think Down syndrome

Question 14

Duodenal atrasia

Answer 14

Think Down syndrome

Question 15

Diaphragmatic hernia

Answer 15

Think T13 and T18

Question 16

Clenched hands and rocker-bottom feet

Answer 16

Think T18

Question 17

Significantly small chest and long bones

Answer 17

Think skeletal dysplasia

Question 18

Oligo- or anhydramnios

Answer 18

Think renal abnormality

Question 19

Polyhydramnios

Answer 19

Think GI blockage

Question 20

Significantly high AFP (>10 MoM AFAFP)

Answer 20

Congenital Finnish Nephrosis

• abnormal renal tubule development
• looks normal on U/S
• extremely high MSAFP
• high AFAFP and negative ACHE
• AR inheritance
• “lethal” condition: don’t survive to transplant

Question 21

Elevated or decreased levels of serum analytes when aneuploidy has been ruled out

Answer 21

Can be indication of adverse outcome, such as pre-eclampsia, preterm labor, low birth weight, increased risk for fetal demise, etc

Increased antenatal screening in third trimester typically recommended

Question 22

Undectectable uE3

Answer 22

<0.15 MoM

Can be an indication of fetal adrenal hypoplasia, anencephaly, Smith Lemli Opitz, and X-linked ichthyosis

Question 23

Common ultrasound findings for T21

Answer 23

Increased NT, echogenic bowel, echogenic intracardiac focus (slight association), short humerus, short femur, dilated renal pelvis, cardiac defect (50% will have some CHD), cystic hygroma with or without hydrops, cerebral ventricular dilation, duodenal atresia

Remember only 50% of babies with Down syndrome have something on U/S while the other 50% do not!

Question 24

Common ultrasound findings for T18

Answer 24

choroid plexus cysts (slight association), clenched hands, rocker bottom feet, delayed growth, heart defects, omphalocele

Question 25

Common ultrasound findings for T13

Answer 25

cleft palate, polydactyly, delayed growth, heart defects, holoprosencephaly

Question 26

Level II Ultrasound/Fetal Anatomy Scan

Answer 26

Offered to many patients between 18-22 weeks

Abnormal in 50% of T21 cases, 70-80% of T18/T13, 80% of spina bifida, and approx 100% of anencephaly

Question 27

What maternal infections make up TORCH?

Answer 27

Toxoplasmosis, Other (syphilis, varicella, parvovirus), Rubella, CMA, Herpes

Question 28

What symptoms are seen with congenital toxoplasmosis?

Answer 28

Ocular lesions/Choroiretinitis (80%), Hydrocephalus, Intracranial calcifications

Note: 85% of infected newborns are asymptomatic at birth, but 90% of these develop some symptoms later in life

Question 29

What symptoms are seen with congenital syphilis?

Answer 29

Bony abnormalities, hepato/splenomegaly, skin lesions, enemia, pseudoparalysis, saddle nose, palate problems, deafness, developmental delay.

Some symptoms arent present until 2 years old

Question 30

What symptoms are seen with congenital rubella syndrome (German measles)?

Answer 30

Deafness (60%), Eye problems (50%; cataracts, retinitis, glaucoma), heart defects, CNS problems (microcephaly, MR 10-20%, encephalitis), thrombocytopenia, hepatosplenomegaly

*Think deaf and blind

Question 31

What symptoms are seen with congenital CMV infection?

Answer 31

Microcephaly, ID,SNHL, chorioretinitis, seizures, intracranial calcifications, hepatosplenomegaly, thrombocytopenia, petrichiae, IUGR, dental problems

Question 32

What symptoms are seen with congenital herpes simplex virus II?

Answer 32

Skin vesicles/scarring, chorioretinitis, microphthalmia, cataract, microcephaly, intracranial calcifications, seizures, encephalomalacia, encephalitis, growth retardation, psychomotor development problems

Question 33

What symptoms are seen with uncontrolled maternal PKU?

Answer 33

global DD (~92%), microcephaly (73%), IUGR (40%), postnatal growth retardation (51%), SAB (24%), cardiac defect (15%), behavioral problems

Question 34

What symptoms are seen with uncontrolled maternal diabetes/diabetic embryopathy?

Answer 34

VACTERL/VATER association: Vertebral anomalies, anal atresia, cardiac abnormalities, TE fistula, Renal abnormalities, limb defects

Also:preterm birth, macrosomia, organomegaly, IUGR, CV defects, skeletal defects, NTDs, respiratory, hematologic, metabolic, GI and renal problems

Question 35

What symptoms are seen with fetal alcohol syndrome?

Answer 35

Craniofacial dysmorphology (microcephaly, short palp fissures, long, smooth philtrum), growth deficiencies, CNS dysfunction (ID, irritability in infancy, hypersensitivity in childhood), skeletal abnormalities (pectus, contractures), cardiac defects, GU defects, renal defects

Question 36

What symptoms are seen with cocaine use during pregnancy?

Answer 36

Neurobehavioral (withdrawel especially), cerebrovascular events resulting in brain damage, growth restriction, congenital anomalies

Most of these secondary to vasoconstriction

Question 37

What are some of the most common symptoms of AED embryopathy?

Answer 37

NTD (1-2% risk; these are folate antagonists)
Ebstein anomaly (1/1000 risk)

Question 38

What are some of the most common symptoms of antihypertensives (ACE inhibitors) used during pregnancy?

Answer 38

1st trimester: 2.7 fold increased risk for CNS and cardiac anomalies
2nd trimester: affected fetal kidney development and function (leads to oligohydramnios and then Potter sequence)

Question 39

What 4 conditions does ACMG suggest individuals with AJ ancestry be screened for?

Answer 39

CF, Canavan, familial dysautonomia, Tay-Sachs

*Also recommends fanconi anemia, neimann-pick, mucolipidosis IV, Gaucher