Gross Aneuploidy

Question 1

Triploidy

Answer 1

● Entire extra set of chromosomes
● 46, XXX or 46, XXY
● Present in 1-2% of conceptions, 10% of miscarriages
● Typically results in miscarriage in the first trimester
o Livebirths have been reported
● Digyny
o Extra set of chromosomes are maternally derived
o Severe asymmetric IUGR with head sparing
o Small placenta
● Diandry
o Extra set of chromosomes are paternally derived
o Large cystic/partial molar placenta
o Normal growth or limited fetal growth restriction
o Maternal serum screening will show 10x higher hCG than expected
o Maternal risk for pre-eclampsia and choriocarcinoma
● Features of triploidy syndrome
o 3,4-syndactyly
o Cystic placenta
● May be detected on NIPT through SNP-method only (Natera)

Question 2

Trisomy 13 (Patau Syndrome)

Answer 2

Extra copy of chromosome 13
● Due to nondisjunction during MATERNAL MEIOSIS I
● Few survive to term, most die within first year of life
● Ultrasound findings:
o Holoprosencephaly,
o Cleft lip
o Double outlet right ventricle
o VSD
o Echogenic kidneys
o Omphalocele
● Maternal serum screening WILL NOT adjust risk for this disorder

Question 3

Trisomy 18 (Edward Syndrome)

Answer 3

● Extra copy of chromosome 18
● Due to nondisjunction during MATERNAL MEIOSIS II
● Few survive to term, most die within first year of life
● Ultrasound findings:
o Clenched fists
o Choroid plexus cysts
o Rocker bottom feet
o IUGR
o Polyhydramnios
o Omphalocele
● Maternal serum screening will show decreased hCG, decreased inhibin A, decreased uE3,
decreased AFP

Question 4

Trisomy 21 (Down Syndrome)

Answer 4

● Extra copy of chromosome 21
● Due to nondisjunction in MATERNAL OR PATERNAL MEIOSIS I
● FTS – Low PAPP-A and High hCG
● Ultrasound findings:
o Increased nuchal translucency in first trimester
o Increased nuchal fold in second trimester (>6.0 mm)
o Structural heart defect (50%)
o Hypoplastic nasal bone
o Echogenic bowel
o Echogenic intracardiac focus (WEAK ASSOCIATION)
● Syndrome features:
33
o Mild to moderate intellectual
disability
o Good social skills
o Congenital heart defects
(~50%) – VSD, ASD, ToF
o Increased risk for leukemia
o Decreased risk for solid
tumors
o Brushfield spots in iris
o GI problems
o Hearing loss
o Hypothyroidism
o Dysmorphic features:
▪ Upslanted palpebral fissures
▪ Epicanthal folds
▪ Sandal gap
▪ Short stature
Brushfield spots

Question 5

Cat Eye Syndrome

Answer 5

Partial trisomy or tetrasomy of chromosome 22
● Associated with a marker chromosome 22
● Usually de novo but parents may be unaffected mosaic
● Syndrome features:
o Coloboma
o Preauricular pits/tags
o Cardiac defects
o Missing or underdeveloped kidneys
o Short stature
o Skeletal problems
o Borderline-to-mild intellectual disability
o Hernia
o Cleft palate
● Clinically similar to DiGeorge and CHARGE, “marker chromosome” may help differentiate
in a question

Question 6

Turner Syndrome

Answer 6

45, X
● Due to nondisjunction in PATERNAL MEIOSIS
● Syndrome features:
o Aortic stenosis/Coarctation
of the aorta
o Obesity
o Amenorrhea
o Streaked ovaries
o Learning difficulties/ADHD
o Horseshoe kidney
o Dysmorphic features:
▪ Short stature
▪ Webbed neck
▪ Widely spaced nipples
▪ Cystic hygroma

Question 7

Klinefelter Syndrome

Answer 7

47, XXY
● Due to nondisjunction in MATERNAL OR PATERNAL MEIOSIS I
● Syndrome features:
o Tall stature
o Normal intelligence – may have reading and speech difficulties
o Feminization at puberty
▪ Gynecomastia
▪ Broad hips
▪ Reduced or absent facial hair
o Reduced fertility
o Hypogonadism
o Increased risk for breast cancer
o Increased risk for thromboembolism

Question 8

XYY Syndrome

Answer 8

47, XYY
● Syndrome features:
o Tall stature
o Developmental delay
o Learning difficulties
o Behavior problems
▪ NO LINK TO INCREASED AGGRESSION
o Normal sexual development