Trisomy 13, 18, and 21

Question 1

What is the genetic basis of Trisomy 13 (Patau syndrome)?

Answer 1

Trisomy 13 is caused by the presence of an extra copy of chromosome 13, most commonly due to meiotic nondisjunction.

Question 2

What are the hallmark clinical features of Trisomy 13?

Answer 2

Clinical features include:

• microphthalmia (mai - krow - thal - mee -uh), eyes are smaller than usual
• cleft lip/palate
• polydactyly
• holoprosencephaly (the left and right sides of the brain do not separate)
• severe intellectual deficits
• cardiovascular defects (ASD, VSD, PDA)
• omphalocele (protrusion through the belly button)

Question 3

What are the first-trimester screening (performed at 9-13 weeks) findings for Trisomy 13 (Patau syndrome)?

Answer 3

Increased nuchal translucency (NT), low PAPP-A, and low β-hCG levels.

Question 4

What are the second-trimester quad screen (performed at 15-22 weeks) findings for Trisomy 13?

Answer 4

Variable findings

The quad screen is less specific for Trisomy 13 compared to Trisomy 21 and 18.

Question 5

What is the prognosis for Trisomy 13?

Answer 5

Most infants with Trisomy 13 die within days to weeks after birth.

Question 6

How is Trisomy 13 diagnosed?

Answer 6

Diagnosis is confirmed with karyotype analysis or fluorescence in situ hybridization (FISH).

Question 7

What is the genetic basis of Trisomy 18 (Edwards syndrome)?

Answer 7

Trisomy 18 is caused by the presence of an extra copy of chromosome 18, most commonly due to meiotic nondisjunction.

Question 8

What are the hallmark clinical features of Trisomy 18?

Answer 8

Clinical features include:

micrognathia (mai - krow -nay -thee -ah), small jaw

low-set ears

prominent occiput

clenched fists with overlapping fingers

cardiovascular defects (e.g., VSD, PDA)

renal abnormalities (e.g., horseshoe kidney)

GI anomalies (e.g., Meckel’s diverticulum, malrotation, diaphragmatic hernia).

Question 9

What are the first-trimester screening (performed at 9-13 weeks) findings for Trisomy 18 (Edwards syndrome)?

Answer 9

Increased nuchal translucency (NT), low PAPP-A, and low β-hCG levels.

Question 10

What are the second-trimester quad screen (performed at 15-22 weeks) findings for Trisomy 18?

Answer 10

Low AFP, low β-hCG, low estriol, and normal or slightly decreased inhibin.

Question 11

What is the prognosis for Trisomy 18?

Answer 11

Most infants with Trisomy 18 die within the first year, and survivors have severe intellectual deficits.

Question 12

How is Trisomy 18 diagnosed?

Answer 12

Diagnosis is confirmed with karyotype analysis or fluorescence in situ hybridization (FISH).

Question 13

What is the genetic basis of Trisomy 21 (Down syndrome)?

Answer 13

Trisomy 21 is caused by an extra copy of chromosome 21, most commonly due to meiotic nondisjunction. Rarely, it results from Robertsonian translocation or mosaicism.

Question 14

What are the characteristic facial features of Trisomy 21?

Answer 14

Facial features include upslanting palpebral fissures, epicanthal folds, flat nasal bridge, flattened midface, redundant nuchal skin, hydrops, small ears, brushfield spots, and a protruding tongue.

Question 15

What is a characteristic feature in down syndrome scene with these patient’s feet?

Answer 15

They’re usually as a gap between the first two toes.

Question 16

What is a common feature seen in a patient with down syndrome when evaluating their hands?

Answer 16

A single palmar crease

Question 17

What are the common a G.I. complications seen with patients with down syndrome particularly on delivery of a neonate?

Answer 17

Hirschsprung disease

Duodenal atresia

Imperforate anus

Esophageal atresia

Question 18

Infants with down syndrome tend to have hypertonia or hypotonia?

Answer 18

hypotonia

Question 19

What are CNS associated medical complications of Trisomy 21?

Answer 19

Complications include intellectual disability, hypotonia, and early-onset Alzheimer disease

Question 20

What are the common cardiovascular issues observed with patients who have down syndrome?

Answer 20

cardiovascular defects:

• AV septal defect
• ASD
• VSD

Question 21

What are the common endocrine disorders seen in patients with down syndrome?

Answer 21

hypothyroidism.

obesity.

Type 1 diabetes mellitus.

Question 22

What are the known hematologic issues in patient with down syndrome?

Answer 22

Increased risk of ALL/AML (+ TdT).

Question 23

Why do patients with down syndrome need a cervical x-ray before any major operation?

Answer 23

Due to atlantoaxial instability.

Question 24

What screening tests are recommended for patients with Trisomy 21?

Answer 24

Screening includes:

• CBC
• TSH
• TTE
• hearing and vision tests
• cervical spine X-rays for atlantoaxial instability

Question 25

How is Trisomy 21 diagnosed?

Answer 25

Diagnosis is confirmed with karyotype analysis or fluorescence in situ hybridization (FISH).

Question 26

What is the life expectancy for Trisomy 21?

Answer 26

With appropriate medical care, individuals with Trisomy 21 can live into their 50s or 60s.

Question 27

What are the first-trimester screening findings for Trisomy 21 (Down syndrome)?

Answer 27

Increased nuchal translucency (NT), low PAPP-A, and high β-hCG levels.

Question 28

What are the second-trimester quad screen findings for Trisomy 21?

Answer 28

Low AFP, high β-hCG, low estriol, and high inhibin.

Question 29

What is the role of cell-free DNA (cfDNA) testing in prenatal aneuploidy screening?

Answer 29

cfDNA testing, performed after 10 weeks of gestation, has high sensitivity and negative predictive value (NPV) for detecting trisomies, but it is not diagnostic.

Question 30

What does reduced AFP (<0.5 MoM) indicate in prenatal screening?

Answer 30

Reduced AFP suggests Trisomy 21 or 18, fetal demise, or incorrect gestational dating.

Question 31

What does increased AFP (>2.5 MoM) indicate in prenatal screening?

Answer 31

Increased AFP suggests open neural tube defects (e.g., anencephaly, spina bifida), abdominal wall defects (e.g., gastroschisis, omphalocele), multiple gestation, or incorrect gestational dating.