Trisomies

Question 1

What is the most common live-born chromosomal anomaly

Answer 1

Down syndrome

Question 2

most common cause of intellectual disability

Answer 2

down syndrome

Question 3

key physical clinical features of Down Syndrome

Answer 3

• flat, wide set NASAL BRIDGE
• low set, small ears
• brachycephaly (flat posterior skull)
• prominent EPICANTHAL folds
• UPSLANTING palpebral fissures
• brushfield spots (white spots on iris)
• short, broad hands
• transverse palmar crease
• “sandal gap”
• DYSTONIA (low muscle tone)
• short stature

Question 4

congenital heart disease in down syndrome

Answer 4

• about 50%

* most commonly endocardial cushion defects (primum ASD or VSD ->holosystolic murmur)

Question 5

GI anomalies in down syndrome

Answer 5

• about 5%

* duodenal atresia or stenosis

Question 6

alzheimer’s in down syndrome

Answer 6

• common, and early onset (<50yo)

* amyloid precursor protein (APP) on chromosome 21

Question 7

malignancy in down syndrom

Answer 7

• increased risk
• 1-1.5 percent
• leukemias

Question 8

most common cause of down syndrome

Answer 8

• meiotic nondisjunction (95%)
  
  • 90% meiosis I
  • 90% extra chromosome from mother

Question 9

rare cause of down syndrome

Answer 9

• robertsonian translocation (2-3%)
• risk does NOT increase with maternal age
• high recurrence risk in families

Question 10

rarest cause of down syndrome

Answer 10

• mitotic error post fertilization (<2%)

* somatic mosaicism

Question 11

fetal karyotype in down syndrome prenatal screening

Answer 11

• invasive and carries risks
• only done in cases when high risk
• 1st trimester -> chorionic villus sampling (from placenta)
• 2nd trimester -> amniocentesis

Question 12

ultrasound testing in down syndrome

Answer 12

• non-invasive, can be predictive but not confirmatory
• small, poorly formed nasal bones
• nuchal translucency (fluid under back of neck)

Question 13

maternal serum testing in down syndrome (1st trimester)

Answer 13

• pregnancy associated plasma protein A (PAPP-A) -> LOW

* β-hCG -> HIGH

Question 14

maternal serum testing in down syndrome (2nd trimester)

Answer 14

• “quad test”
• α-fetoprotein (AFP) -> LOW
• estriol (uE3) -> LOW
• β-hCG -> HIGH
• Inhibin-A -> HIGH

Question 15

commonalities of all trisomies

Answer 15

• associated with maternal age
• commonly due to meiotic NDJ
• intellectual disabilities
• physical deformities
• congenital heart defects

Question 16

trisomies in order of how common they are (live births)

Answer 16

Down syndrome (21) > Edward syndrome (18) > patau syndrome (13)

Question 17

male and female occurrence of Edward syndrome

Answer 17

3:1 female:male

Question 18

key physical clinical features of Edward syndrome

Answer 18

• low birth weight
• SMALL HEAD, prominent occiput
• low set ears
• SMALL JAW, MOUTH
• clenched fist w/ overlapping fingers
• “rockerbottom” feet

Question 19

congenital heart disease in Edward syndrome

Answer 19

• about 50%
• VSD
• patent ductus arteriosus (PDA)

Question 20

GI defects in Edward syndrome

Answer 20

• about 75%
• meckel’s diverticulum (most common)
• malrotation
• omphalacele

Question 21

survival rates with edward syndrome

Answer 21

• many die in utero
• 50% die in 2 weeks
• only 5-10% survive first year

Question 22

ultrasound in edward syndrome diagnosis prenatally

Answer 22

• usually can diagnose physical deformities
  
  • limb defects
  • congenital heart defects

Question 23

maternal serum testing in edward syndrome (1st trimester)

Answer 23

• pregnancy associated plasma protein A (PAPP-A) -> LOW

* β-hCG -> LOW

Question 24

maternal serum testing in edward syndrome (2nd trimester)

Answer 24

• “quad test”
• α-fetoprotein (AFP) -> LOW
• estriol (uE3) -> LOW
• β-hCG -> LOW
• Inhibin-A -> LOW

Question 25

most severe trisomy

Answer 25

patau syndrome (13)

Question 26

detection of patau syndrome by ultrasound

Answer 26

90% can be diagnosed

Question 27

key physical clinical features of patau syndrome

Answer 27

• microphthalmia or anophthalmia
• cleft lip/palate
• post-axial (away from midline of body) polydactyly
• holoprosencephaly (hemispheres of brain)

Question 28

congenital heart disease in patau syndrome

Answer 28

• about 80%
• VSD
• ASD
• patent ductus arteriosus (PDA)

Question 29

survival rates with patau syndrome

Answer 29

• most die in utero
• median survival after birth ~7 days
• 91% die within first year

Question 30

maternal serum testing in patau syndrome (1st trimester)

Answer 30

•pregnancy associated plasma protein A (PAPP-A) -> LOW
•β-hCG -> LOW
(usually diagnosed by US though)