Prenatal 2 Flashcards
Tumor Surveillance for BWS
Abdominal US and AFP screening every 3 mth to age 8
- 50% tumor risk for IC1 maternal Gain of methylation
Genetic testing options for BWS
- Methylation studies** key
- Sequencing and del/dup of CDKN1C
- CMA (ID’s 9% of BWS)
- Karyotype (IDs 1% of BWs)
Angelman Syndrome
-Causes
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”
Wolf-Hirschhorn Syndrome
- Cause
- Testing
4p- (del of small arm)
60%: de novo
40%: unbalanced translocation
CMA, FISH, Karyotype
Smith-Magenis Syndrome
- Cause
- Testing
Cause:
17p11.2 del
RAI1 single gene mt
de novo mostly
Testing:
90%: CMA
10%: RAI1 sequencing (del-dup)
Miller-Dieker Syndrome
-Cause
17p13.3 del
AD
LIS1 gene- usu sporadic, parental transloc. possible
Monosomy 1p36
(1p36del syndrome)
-Causes
-Testing
Testing: CMA is BEST
-Karyotype/ FISH
Joubert syndrome
Testing
Key features`
Sequence analysis of associated genes
**Molar tooth sign on MRI
Hypotonia
DD
Atypical eye movements
NF1
-Causes
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
Differential for increased NT on U/S
-Testing
- 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
- Chrom analysis
- Noonan sequencing test
- PTPN11
- SOS1
- RAF1
Differential for abnormal ductus venous flow on doppler U/S
ductus venous flow
- Blood flow through the umbilical cord
- Measured in 1st trimester
Reversal of the flow: Increased risk for
- Chromosome abnorm
- CHD
- Twin-twin transfusion syndrome
Differential for hydrops on U/S
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
Holoprosencephaly
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
Cleft Lips +/- Cleft palate is seen on U/S
-What is the differential?
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
congenital diaphragmatic hernia (CDH) is seen on U/S
-Differential?
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
Duodenal atresia or stenosis is seen on US
-Differential?
- Fetal bowel obstruction
- “Double-Bubble”
- in 3rd trimester: also seen with polyhydramnios
20-35%: T21
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
- Causes
- Hallmark U/S features
Causes: PKHD1 gene
AR
U/S:
- Bilateral, enlarged, echogenic kidneys
- Oligohydramnios
Oligohydraminos –> pulmonary hypoplasia )lack of cells) –> prenatal mortality
7q11. 23 duplication syndrome
- Features
- Causes
-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)
Transient neonatal DMI
- Features
- Causes
-Features
Hyperglycemia in 1st 6 mths
IUGR
-Causes Imprinting disorder Paternal UPD 6q24 Maternal hypomethylation Single gene disorders
Beals Syndrome (Congenital Contractural Arachnodactyly)
- Features
- Causes
-Features "MFS-like appearence" Tall/thin, arachnodactylyl *Camptodactyly (BENT) Pectus Jt contractures *"Crumpled ears" muscular hypoplasia aortic dilation/dissection
-Causes: AD
FBN2
Sphrintzen-Goldberg Syndrome / “Marfaniod craniosynostosis syndrome”
-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
Vertical transmission Hepatitis B & C
B: if active infection, there is significantly increased risk of VT
C: usually there is no significant increased risk
DAZ1 Gene
Associated with Azoospermia when deleted
