BONUS WEEKEND QUESTION #5

TOPIC: Principles of Genetics

Dec 07, 2024

Today’s bonus weekend question will test your ability to identify and classify a commonly tested genetics topic.

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A 7-year-old boy is brought to the pediatrician due to developmental delay, learning difficulties, and frequent infections. Physical examination reveals a broad nasal bridge, short stature, and clinodactyly of the fifth fingers. Family history shows that several male relatives on his mother’s side have experienced similar symptoms, while no affected individuals are present in his father’s family. Genetic testing reveals an abnormal karyotype involving an expansion in a specific gene, which codes for a protein critical in cellular signaling pathways. Which of the following best describes the inheritance pattern of this condition?

A) Autosomal recessive
B) Autosomal dominant
C) X-linked recessive
D) Mitochondrial inheritance
E) X-linked dominant

Detailed Breakdown of Answers + Correct Answer Below ⏬

ANSWER + QUESTION BREAKDOWN

It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our 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 best describes the inheritance pattern of this condition?”

Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Identify the condition in question; 2nd: Identify the condition’s mode of inheritance.

Step 3: Read the vignette carefully and ask yourself: “Based on my suspicion for ____________________, its mode of inheritance is _________________.”

Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.

GENERAL ANALYSIS

This vignette describes a 7-year-old boy with developmental delay, learning difficulties, and frequent infections, along with physical features such as a broad nasal bridge, short stature, and clinodactyly. The family history shows that several male relatives on his mother’s side have similar symptoms, but no affected individuals are present in his father’s family. Genetic testing reveals an abnormal karyotype involving an expansion in a specific gene related to cellular signaling pathways.

ANSWER CHOICES:

CHOICE A: Autosomal recessive

Explanation: Autosomal recessive inheritance requires two copies of a mutated gene (one from each parent) for the condition to manifest. Both males and females can be equally affected. The family history shows that only males on the maternal side are affected, which is more consistent with an X-linked pattern than autosomal recessive inheritance.

CHOICE B: Autosomal dominant

Explanation: Autosomal dominant inheritance requires only one copy of a mutated gene for the condition to manifest. Both males and females can be equally affected. The condition appears to be affecting only males on the maternal side, which is more consistent with X-linked inheritance rather than autosomal dominant inheritance.

CHOICE C: X-linked recessive

Explanation: In X-linked recessive inheritance, males are more commonly affected because they have only one X chromosome. Females can be carriers without showing symptoms. Affected males inherit the mutated gene from their mothers. The family history (affected males on the maternal side) and lack of affected individuals on the father’s side strongly suggest an X-linked recessive pattern. Additionally, developmental delay and frequent infections are common features of some X-linked recessive disorders (e.g., Fragile X syndrome or immunodeficiency syndromes).

CHOICE D: Mitochondrial inheritance

Explanation: Mitochondrial inheritance involves genes passed down from the mother through mitochondrial DNA. Both males and females can be affected, but only females pass the condition to their offspring. Mitochondrial inheritance would affect male and female offspring equally, which does not match this case where only males are affected.

CHOICE E: X-linked dominant

Explanation: In X-linked dominant inheritance, both males and females can be affected, but affected males typically have more severe symptoms. Affected females can pass the condition to both male and female offspring. While this pattern could explain some cases involving both sexes, the family history here suggests an X-linked recessive pattern because only males are affected.

FINAL VERDICT…

The most likely inheritance pattern for this patient’s condition is X-linked recessive, based on the family history of multiple affected males on the maternal side and no affected individuals on the paternal side. This pattern is characteristic of many genetic conditions that affect cellular signaling pathways, resulting in developmental delays or learning difficulties in males.

Key Concepts:

The family history suggests an X-linked inheritance pattern, as the condition affects multiple males on the maternal side (consistent with X-linked recessive inheritance).
The genetic abnormality involves a gene that is critical for cellular signaling pathways, which is commonly seen in certain X-linked disorders.
The combination of developmental delay, learning difficulties, and recurrent infections is characteristic of some X-linked genetic disorders.

CORRECT ANSWER: C) X-linked recessive