General Population Screening

Question 1

Screening by ethnicity

Answer 1

●Caucasian – Cystic fibrosis
●African-American – Sickle cell disease
●Italians/Mediterranean – Beta-thalassemia
●Asians – Alpha-thalassemia
●Ashkenazi Jewish
oBRCA 3-site panel
▪BRCA1 – 185delAG, 5382insC
▪BRCA2 – 6174delT
oGaucher disease is the most common inherited disease in the Ashkenazi Jewish population
oOther disease seen on AJ screening panels
▪Canavan, Bloom, Tay-sachs, CF, Mucopolylipidosis IV, maple syrup urine disease, Fanconi anemia, GSD type 1a, Niemann-Pick A, Joubert type 2, familial dysautonomia, etc.

Question 2

Criteria for inclusion on NBS

Answer 2

oTreatable
oDetectable in the newborn period
oPre-symptomatic initiation of treatment is beneficial
oResources are available for diagnosis/treatment/follow-up
oAvailability of a simple method for sample collection
oEvidence of substantial public acceptance and benefit
oSuitable and simple test methods
oAcceptable costs

Question 3

Features ideal screening tests

Answer 3

●High sensitivity – identifies a high % of affected individuals
●High specificity – low number of false positives
●Early availability – increase options and safety of options
●Easy and inexpensive

Question 4

First Trimester Screening

Answer 4

●Maternal serum levels of PAPP-A and hCG + ultrasound
●ADJUSTS RISK for trisomy 18 and trisomy 21
●Trisomy 21 shows elevated hCG and decreased PAPP-A
●Trisomy 18 shows decreased hCG and decreased PAPP-A
●Results can be affected by maternal age, weight, race, and gestational diabetes

Question 5

Quad/multiple marker screen

Answer 5

●Maternal serum levels of hCG, inhibin A, uE3, AFP
●ADJUSTS RISK for trisomy 18, trisomy 21, and neural tube defects (NTD)
●Trisomy 18 will show decreased hCG, decreased inhibin A, decreased uE3, decreased AFP
●Trisomy 21 will show increased hCG, increased inhibin A, decreased uE3, decreased AFP
●NTD increased risk when MoM (multiple of the median) for AFP is >2.0
●Results can be affected by maternal age (except AFP), weight, race, and gestational diabetes
●Steroid sulfatase deficiency and SLO should be considered with very low uE3 levels

Question 6

NIPT

Answer 6

●Can detect some trisomies (typically 13, 18, 21, may detect others)
●Can detect some microdeletions and microduplications
●Can detect sex chromosome aneuploidy (to an extent)
●May detect triploidy (SNP-based method only (Natera))

Question 7

Ultrasound findings in NTD/ventral wall defects

Answer 7

oSpina bifida – Lemon sign (Chiari II malformation), banana sign (cerebellum)
oAnencephaly
oGastroschisis

Question 8

Other Ultrasound findinds

Answer 8

• Double bubble – duodenal atresia
• 2-vessel cord – may be a normal pregnancy, sometimes seen in trisomy 21
• Missing/absent limbs or digits - amniotic band
• Ventriculomegaly
• Congenital absence of the cavus septum pellucidum (CSP) – Septo-optic dysplasia
• Echogenic bowel – may be due to maternal cytomegalovirus (CMV) infection, cystic fibrosis, Down syndrome, or bowel obstruction/stenosis
• Club foot
• Cleft lip (palate is usually not detectable on US)
• Structural heart defects
• Endocardial cushion defect – poorly formed septums of the heart – 60% have trisomy 21
• Ebstein’s anomaly – improperly formed triscupid valve

Question 9

First Trimester Screening

Answer 9

● Maternal serum levels of PAPP-A and hCG + ultrasound
● ADJUSTS RISK for trisomy 18 and trisomy 21
● Results can be affected by maternal age, weight, race, and gestational diabetes

Question 10

FTS: Trisomy 21 shows ___ hCG and ___ PAPP-A

Answer 10

●Trisomy 21 shows elevated hCG and decreased PAPP-A

Question 11

FTS: Trisomy 18 shows ___ hCG and ___ PAPP-A

Answer 11

Trisomy 18 shows decreased hCG and decreased PAPP-A

Question 12

Quad Screen/Multiple Marker Screen

Answer 12

● Maternal serum levels of hCG, inhibin A, uE3, AFP
● ADJUSTS RISK for trisomy 18, trisomy 21, and neural tube defects (NTD)
● Results can be affected by maternal age (except AFP), weight, race, and gestational diabetes

Question 13

MMS: Trisomy 18 will show ___ hCG, ___inhibin A, ___ uE3, ____ AFP

Answer 13

●Trisomy 18 will show decreased hCG, decreased inhibin A, decreased uE3, decreased AFP

Question 14

MMS: Trisomy 21 will show___ hCG, ___inhibin A, ___ uE3, ___ AFP

Answer 14

●Trisomy 21 will show increased hCG, increased inhibin A, decreased uE3, decreased AFP

Question 15

Steroid sulfatase deficiency and SLO should be considered with ____ uE3 levels

Answer 15

● Steroid sulfatase deficiency and SLO should be considered with very low uE3 levels

●NTD increased risk when MoM (multiple of the median) for AFP is >2.0