Archive Of Standardized Exam Questions: Down Syndrome (Trisomy 21)


This page is dedicated to organizing various examples of standardized exam questions whose answer is down syndrome (trisomy 21). While this may seem a odd practice, it is useful to see multiple examples of how down syndrome will be characterized on standardized exams (namely the boards and the shelf exams). This page is not meant to be used as a tradition question bank (as all of the answers will be the same), however seeing the classic “test” characterization for a disease is quite valuable.


When it comes to standardized exams, each condition has its own “code” marked by key buzzwords, lab findings, clues, etc. If you are well versed in this code you will be able to more quickly identify the condition that is being discussed, and get the right answer on the exam you are taking. Below is the “code” for down syndrome

Chief Complaints:

  • Cognitive impairment
  • Developmental delay

Clinical Workup:

  • Facial dysmorphism: upslanting palpebral fissures, flat nasal bridge
  • Single palmar crease: pretty much only seen in patients with this condition on standardized tests.
  • Cardiac defects: murmurs can be heard, echo can show structural abnormality
  • Hormone changes in mother during pregnancy:
    1. Maternal serum alpha-fetoprotein: Decreased
    2. Beta-hCG: Increased
    3. Unconjugated estriol: Decreased
    4. Inhibin A: Increased
  • Ultrasound findings during pregnancy:
    • Duodenal bubble (signifying possible duodenal atresia)

Question # 1

A 5 year old girl is brought to the clinic by her parents because of difficulty learning. Her parents are concerned that she is not learning as quickly as the other students in her kindergarten class. She is not able to do simple homework assignments, and even struggles to write the alphabet. Her teacher believes she is a happy and eager to please child, but has also commented that she has trouble learning. The child appears to enjoy going to school. She wears glasses. She is at the 35th percentile for height and 70th percentile for weight. Her vital signs are within normal limits. Her physical exam reveals epicanthal folds. A grade 2/6 murmur is here at the left sternal border. She is unable to run, but has difficulty climbing stairs without placing both feet on each step. She is unable to hop on one foot. She can repeat the alphabet, but can only identity half of it’s letters. What is the most likely diagnosis?

Explanation # 1

Cognitive impairment + abnormal facial features + cardiac abnormalities = down syndrome

Question # 2

A 26 month old adopted girl is brought to the clinic with concerns of developmental delay. She is not walking independently, and is not yet talking. She was born at term to a 42 year old woman who was gravida 3, para 2, aborta 1. There is no information available about the pregnancy or the delivery. The patient is in the 35th percentile for length and the 75th percentile for weight. The physical exam reveals epicanthal folds, a prominent tongue, small/low set ears, and short extremities. Formal testing reveals an IQ of 62. What is the likely cause of this patient’s condition?

Explanation # 2

Developmental delay + facial abnormalities + cognitive impairment = down syndrome

Question # 3

A 38 year old woman, G2P1, comes to the clinic for a routine prenatal visit. She is 16 weeks pregnant based upon her last menstrual period. She has been married for the past 10 years and has a healthy 6 year old son. The patient is doing well and has no family history of genetic disorders, intellectual disability, development delay, or autism. She has not been taking her prenatal vitamins because of “morning sickness”. Her lab results are as follows:

  • Maternal serum alpha-fetoprotein: Decreased ***
  • Beta-hCG: Increased ***
  • Unconjugated estriol: Decreased ***
  • Inhibin A: Increased ***

What diagnosis most likely explains these laboratory results?

Explanation # 3

Decreased serum alpha-fetoprotein + increased beta hCG + decreased unconjugated estriol + inhibit A increased = down syndrome

Question # 4

A 18 year old primigravid patient comes to the physician because she has noticed decreased fetal movements over the past 3 days. She does not know the date of her last menstrual period, and has only been at one previous prenatal visit. Physical examination shows a uterus consistent with a 32 week gestation. Ultrasound estimates the gestational age as 31 weeks. There is a duodenal bubble and flaccid tone of the fetus. What is a condition that might explain this presentation?

Explanation # 4

Duodenal bubble (signifying duodenal atresia)  = down syndrome

Question # 5

A newborn female undergoes a delivery that was unremarkable. A physical exam reveals a flat nasal bridge, mid face hypoplasia, and a single palmar crease bilaterally. A cardiac exam demonstrates the presence of a holosystolic blowing murmur that is best auscultated along the sternal border. What is the likely diagnosis in this patient?

Explanation # 5

Abnormal facial features + single palmar crease + cardiac murmur = down syndrome

Question # 6

Shortly after being born, an infant male is evaluated by the pediatrician on the L/D service. He is in the 10th percentile for both weight and height and his vital sings are within normal limits. A physical exam reveals upslanting palpebral fissures and a protruding tongue. A harsh systolic murmur is auscultated at the left sternal border. An echocardiogram is performed and reveals that this child has a ventricular spatial defect. what is the likely diagnosis in this patient?

Explanation # 6

Abnormal facial features  + cardiac abnormalities (septal defect) = down syndrome

Question # 7

A 40 year old woman struggles to conceive a child for over a year with her partner. She has a past history of pelvic inflammatory disorder and has scarred fallopian tubes. Finally she is able to become pregnant and gives birth to an infant boy. After delivery the child is examined and found to have a flat nasal bridge and low set ears. A karyotype analysis is ordered on the cild and is shown below:

Image source

What is the diagnosis in this patient?

Explanation # 7

Abnormal facial features + trisomy 21 seen on karyotype = down syndrome

Question # 8

A newborn male is evaluated in the nursery soon after delivery. The delivery was uncomplicated and his mother is 42 years old has no remarkable past medical history. The child’s vitals are within normal limits. A physical exam reveals epicanthal folds, slanted palpebral fissures, and a single palmar crease. The patient’s abdominal exam reveals the presence of an umbilical hernia. What is the likely diagnosis in this patient?

Explanation # 8

Abnormal facial features + single palmar crease = down syndrome

Question # 9

A newborn infant girl is evaluated soon after delivery. She is found to have a harsh, holosystolic murmur, and a head and neck exam reveals flat facial features, small low set ears, and a protruding tongue. The infant’s vital signs are within normal limits. What is a possible diagnosis in this patient?

Explanation # 9

Cardiac abnormalities (murmur) + abnormal facial features = down syndrome


Many questions on standardized exams go beyond simply recognizing the underlying condition. Often there are specific testable facts regarding some aspect of the disease’s pathophysiology/management/clinical implications that are commonly asked. Some of these are listed below:


  • Extra copy of 21st chromosome/21st chromosome genes that can occur by three major mechanism:
    1. Meiotic non-disjunction
    2. Unbalanced translocation
    3. Mosaicism




Page Updated: 09.17.2016