USMLE PRACTICE QUESTION #86
TOPIC: GI / Genetics
Today’s question will test your understanding of a commonly tested GI/Genetics question.
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A 4-day-old male infant is brought to the pediatrician by his parents due to a lack of bowel movements since birth. The parents also report that their baby has had episodes of projectile vomiting and a distended abdomen. On physical examination, the infant has a temperature of 98.6°F (37°C), heart rate of 120 beats/min, respiratory rate of 36 breaths/min, and blood pressure of 60/40 mmHg. The abdomen is distended and tender to palpation. Rectal examination reveals an explosive release of stool and flatus. A barium enema reveals a narrowed segment of the colon. Which of the following loss-of-function mutations is most commonly associated with the infant’s condition?
A) Mutation in the SMAD4 gene
B) Mutation in the APC gene
C) Mutation in the TP53 gene
D) Mutation in the RET gene
E) Mutation in the NF1 gene
F) Mutation in the COL3A1 gene
G) Mutation in the CFTR gene
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
The MENTAL MODEL used to answer this question comes from our detailed test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following loss-of-function mutations is most commonly associated with the infant’s condition?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Identify the disorder, and 2nd: Identify the mutation associated with the disorder.
Step 3: Read the vignette carefully and ask yourself: “Which gene mutation causes this condition?”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
The clinical presentation of the 4-day-old male infant with lack of bowel movements since birth, projectile vomiting, abdominal distension, and an explosive release of stool and flatus upon rectal examination, along with a narrowed segment of the colon on a barium enema, is highly suggestive of Hirschsprung disease. This condition is caused by the absence of ganglion cells in the distal colon, leading to a functional obstruction.
ANSWER CHOICES:
CHOICE A: Mutation in the SMAD4 gene
Explanation: SMAD4 mutations are linked to juvenile polyposis syndrome.
CHOICE B: Mutation in the APC gene
Explanation: APC gene mutations lead to colorectal polyps and cancer, not congenital bowel obstruction like Hirschsprung disease.
CHOICE C: Mutation in the TP53 gene
Explanation: TP53 mutations are involved in cancer development, not Hirschsprung disease.
CHOICE D: Mutation in the RET gene
Explanation: The RET gene plays a crucial role in the development of the enteric nervous system, and mutations in this gene are commonly associated with Hirschsprung disease.
CHOICE E: Mutation in the NF1 gene
Explanation: NF1 mutations cause neurofibromas and other tumors but are not linked to Hirschsprung disease.
CHOICE F: Mutation in the COL3A1 gene
Explanation: COL3A1 mutations affect connective tissue integrity but are not associated with Hirschsprung disease. This mutation is associated with Ehlers-Danlos syndrome (vascular type).
CHOICE G: Mutation in the CFTR gene
Explanation: CFTR mutations cause cystic fibrosis, which can lead to meconium ileus but not Hirschsprung disease.
FINAL VERDICT…
Hirschsprung disease is a congenital condition characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the distal colon, resulting in a lack of peristalsis and functional obstruction.
The RET gene plays a crucial role in developing the enteric nervous system, and mutations in this gene are commonly associated with Hirschsprung disease.
The clinical findings of delayed passage of meconium, abdominal distension, and explosive stool release after rectal examination (referred to as the "squirt sign") are classic for this condition.
CORRECT ANSWER: D) Mutation in the RET gene
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That’s it for question 86!
See ya tomorrow 👋