Prenatal 2

Question 1

Tumor Surveillance for BWS

Answer 1

Abdominal US and AFP screening every 3 mth to age 8

- 50% tumor risk for IC1 maternal Gain of methylation

Question 2

Genetic testing options for BWS

Answer 2

1. Methylation studies** key
2. Sequencing and del/dup of CDKN1C
3. CMA (ID’s 9% of BWS)
4. Karyotype (IDs 1% of BWs)

Question 3

Angelman Syndrome

-Causes

Answer 3

Normal: Maternally expressed, Paternally imprinted
AS:
70%: Maternal del 15q11.2** (most severe)
11%: LOF of maternal UBE3A (needed for protein degradation in brain)
10%: unknown genetic cause
5%: Paternal UPD 15q11.2
Angelman - imprinting defect when only paternal is expressed: “ALL MAN”

Question 4

Wolf-Hirschhorn Syndrome

• Cause
• Testing

Answer 4

4p- (del of small arm)
60%: de novo
40%: unbalanced translocation

CMA, FISH, Karyotype

Question 5

Smith-Magenis Syndrome

• Cause
• Testing

Answer 5

Cause:
17p11.2 del
RAI1 single gene mt
de novo mostly

Testing:
90%: CMA
10%: RAI1 sequencing (del-dup)

Question 6

Miller-Dieker Syndrome

-Cause

Answer 6

17p13.3 del
AD
LIS1 gene- usu sporadic, parental transloc. possible

Question 7

Monosomy 1p36
(1p36del syndrome)
-Causes
-Testing

Answer 7

Testing: CMA is BEST

-Karyotype/ FISH

Question 8

Joubert syndrome
Testing
Key features`

Answer 8

Sequence analysis of associated genes

**Molar tooth sign on MRI
Hypotonia
DD
Atypical eye movements

Question 9

NF1

-Causes

Answer 9

Due to NF1 variants (AD)
50%: de novo
5%: 17q11.2 del

Entire NF1 gene del: severe phenotype: higher risk for ID, facial differences
2x higher incidence for malignant peripheral nerve sheath tumor

Question 10

Differential for increased NT on U/S

-Testing

Answer 10

• Taken in 1st trimester: 10-13w6d
• > 3mm : increased risk for adverse outcomes

Aneuploidy (T21, T18, T13, triploidy, XO)
Other chrom anomalies
Skeletal dysplasia
CHD/pulmonary defects
Maternal/congenital infection
Metabolic /hematologic disorders
Noonan syndrome

1. Chrom analysis
2. Noonan sequencing test
   - PTPN11
   - SOS1
   - RAF1

Question 11

Differential for abnormal ductus venous flow on doppler U/S

ductus venous flow

Answer 11

• Blood flow through the umbilical cord
• Measured in 1st trimester

Reversal of the flow: Increased risk for

• Chromosome abnorm
• CHD
• Twin-twin transfusion syndrome

Question 12

Differential for hydrops on U/S

Answer 12

Abnormal fluid accumulation
Can be:
-immune (b/c of RBC alloimmunization)
-nonimmune (NIHF)

NIHF:

• CDH (Congenital diaphragmatic hernia)
• T21, T13, T18, triploidy, Turner
• Hematologic (alpha-thal)
• fetal malformation
• tumors
• viral infection
• placental abnormality

-NIHF fetus- Women: risk for dvping “Mirror Syndrome”: preeclampsia

Question 13

Holoprosencephaly

Answer 13

brain fails to separate into cerebral hemispheres
Lobar > semilobar > alobar (least severe)

50% risk: T18/T13
Viral infection
Mat DM
Mat ETOH
Genetic: sporadic, X-linked, AR, AD

Question 14

Cleft Lips +/- Cleft palate is seen on U/S

-What is the differential?

Answer 14

80%: unilateral CL (left-side)
>80%: CL+ CP

70%: isolated, not associated with syndrome

30%: see with other features, >200 syn associated

Slightly increased risk for T18, T13 but usu not isolated

Question 15

congenital diaphragmatic hernia (CDH) is seen on U/S

-Differential?

Answer 15

Hernia occurs which allows the abdominal contents to seep into chest cavity (left side mostly)

• if these also happen= prognosis is worse:
• LIVER is herniated upward
• Lung:head ratio
• Polyhydraminos

40%: CHD present too

25%: T13, T18, T21, tetrasomy 12p

Question 16

Duodenal atresia or stenosis is seen on US

-Differential?

Answer 16

• Fetal bowel obstruction
• “Double-Bubble”
• in 3rd trimester: also seen with polyhydramnios

20-35%: T21

Question 17

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

• Causes
• Hallmark U/S features

Answer 17

Causes: PKHD1 gene
AR

U/S:

• Bilateral, enlarged, echogenic kidneys
• Oligohydramnios

Oligohydraminos –> pulmonary hypoplasia )lack of cells) –> prenatal mortality

Question 18

7q11. 23 duplication syndrome
- Features
- Causes

Answer 18

-Features
Learning difficulty
delated milestones
seizures
low-avg IQ
anxiety/behavioral/ADHD/ASD
heart defects
macrocephaly, straight eyebrows, flat face, dental

-Causes
Duplication of 7q11.23

opposite of Williams syn (deletion)

Question 19

Transient neonatal DMI

• Features
• Causes

Answer 19

-Features
Hyperglycemia in 1st 6 mths
IUGR

-Causes
Imprinting disorder
Paternal UPD 6q24
Maternal hypomethylation
Single gene disorders

Question 20

Beals Syndrome (Congenital Contractural Arachnodactyly)

• Features
• Causes

Answer 20

-Features
"MFS-like appearence"
Tall/thin, arachnodactylyl
*Camptodactyly (BENT)
Pectus
Jt contractures
*"Crumpled ears"
muscular hypoplasia
aortic dilation/dissection

-Causes: AD
FBN2

Question 21

Sphrintzen-Goldberg Syndrome / “Marfaniod craniosynostosis syndrome”

Answer 21

-Features
*craniosynostosis (premature suture closure)
*club foot
*ID
*CHD: aortic root dilation, MVP, BAV
Tall
arachnodactylyl/camptodactyly
pectus
scoliosis
jt hypermobility/contractures
Brain anomalies (hydrocephaly, ventricle dilation, chiari malformation)
abdominal wall defects
myopia
cryptochidism
bifid uvula/CP

Overlapping features with LDS

-Causes
SKI: gene sequencing

Question 22

Vertical transmission Hepatitis B & C

Answer 22

B: if active infection, there is significantly increased risk of VT
C: usually there is no significant increased risk

Question 23

DAZ1 Gene

Answer 23

Associated with Azoospermia when deleted