Prenatal Genetics Flashcards
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?
10%
If level III mosaicism is reported out on a prenatal sample, what is the likelihood that it represents true mosaicism in the fetus?
80%
First Trimester Screening
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
Quad Screen
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!
Decreased PAPP-A, Increased free b-hCG, Increased NT
FTS: Screen positive for Down syndrome
Decreased PAPP-A, Decreased b-hCG, Increased NT
FTS: Screen positive for grouping of T13/T18
Decreased AFP, Increased hCG, Decreased uE3, Increased DIA
Quad screen: Screen positive for Down syndrome
Decreased AFP, Decreased hCG, Decreased uE3,
Quad screen: Screen positive for T18
Elevated AFP
Screen positive for ONTD
Midline defects (ex. holoprosencephaly, midline cleft, omphalocele)
Think T13
Clubfoot and hydrocephalus and/or fruit in the brain
Think ONTD
Cystic hygroma
Think hydrops and Turner syndrome and Down syndrome
AV canal/endocardial cushion defect
Think Down syndrome
Duodenal atrasia
Think Down syndrome
Diaphragmatic hernia
Think T13 and T18
Clenched hands and rocker-bottom feet
Think T18
Significantly small chest and long bones
Think skeletal dysplasia
Oligo- or anhydramnios
Think renal abnormality
Polyhydramnios
Think GI blockage
Significantly high AFP (>10 MoM AFAFP)
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
Elevated or decreased levels of serum analytes when aneuploidy has been ruled out
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
Undectectable uE3
<0.15 MoM
Can be an indication of fetal adrenal hypoplasia, anencephaly, Smith Lemli Opitz, and X-linked ichthyosis
Common ultrasound findings for T21
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!
Common ultrasound findings for T18
choroid plexus cysts (slight association), clenched hands, rocker bottom feet, delayed growth, heart defects, omphalocele
Common ultrasound findings for T13
cleft palate, polydactyly, delayed growth, heart defects, holoprosencephaly
Level II Ultrasound/Fetal Anatomy Scan
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
What maternal infections make up TORCH?
Toxoplasmosis, Other (syphilis, varicella, parvovirus), Rubella, CMA, Herpes
What symptoms are seen with congenital toxoplasmosis?
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
What symptoms are seen with congenital syphilis?
Bony abnormalities, hepato/splenomegaly, skin lesions, enemia, pseudoparalysis, saddle nose, palate problems, deafness, developmental delay.
Some symptoms arent present until 2 years old
What symptoms are seen with congenital rubella syndrome (German measles)?
Deafness (60%), Eye problems (50%; cataracts, retinitis, glaucoma), heart defects, CNS problems (microcephaly, MR 10-20%, encephalitis), thrombocytopenia, hepatosplenomegaly
*Think deaf and blind
What symptoms are seen with congenital CMV infection?
Microcephaly, ID,SNHL, chorioretinitis, seizures, intracranial calcifications, hepatosplenomegaly, thrombocytopenia, petrichiae, IUGR, dental problems
What symptoms are seen with congenital herpes simplex virus II?
Skin vesicles/scarring, chorioretinitis, microphthalmia, cataract, microcephaly, intracranial calcifications, seizures, encephalomalacia, encephalitis, growth retardation, psychomotor development problems
What symptoms are seen with uncontrolled maternal PKU?
global DD (~92%), microcephaly (73%), IUGR (40%), postnatal growth retardation (51%), SAB (24%), cardiac defect (15%), behavioral problems
What symptoms are seen with uncontrolled maternal diabetes/diabetic embryopathy?
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
What symptoms are seen with fetal alcohol syndrome?
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
What symptoms are seen with cocaine use during pregnancy?
Neurobehavioral (withdrawel especially), cerebrovascular events resulting in brain damage, growth restriction, congenital anomalies
Most of these secondary to vasoconstriction
What are some of the most common symptoms of AED embryopathy?
NTD (1-2% risk; these are folate antagonists) Ebstein anomaly (1/1000 risk)
What are some of the most common symptoms of antihypertensives (ACE inhibitors) used during pregnancy?
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)
What 4 conditions does ACMG suggest individuals with AJ ancestry be screened for?
CF, Canavan, familial dysautonomia, Tay-Sachs
*Also recommends fanconi anemia, neimann-pick, mucolipidosis IV, Gaucher
