USMLE® Step 1 Question of the Day: Inheritance patterns

Test your knowledge with this USMLE Step 1 Question of the Day. A 3-year-old boy is brought to the office due to difficulty keeping up with other children at daycare. The physical examination reveals enlarged calves, and a genetic condition is suspected. Review the patient's family pedigree and determine the most likely inheritance pattern for this condition.

A 3-year-old boy is brought to the office by his parents because of difficulty keeping up with other children at daycare. The parents report that he has difficulty climbing stairs and seems more tired and less interested in active play. The patient has a history of upper respiratory tract infections twice in the last year. Temperature is 37°C (98.6°F), pulse is 70/min, respirations are 19/min and blood pressure is 100/60 mmHg. Physical examination shows enlarged and nontender calves bilaterally. The rest of the examination is unremarkable. A genetic condition is suspected. The patient’s family pedigree with respect to this condition is shown with the red arrow indicating his position within the family. 

Assuming that the genetic condition demonstrates complete penetrance, which of the following inheritance patterns is most likely in this patient? 

A. X-linked dominant 

B. X-linked recessive 

C. Autosomal dominant 

D. Autosomal recessive 

E. Mitochondrial 

Scroll down for the correct answer!

The correct answer to today's USMLE® Step 1 Question is...

B. X-linked recessive 

Before we get to the Main Explanation, let's look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!

Incorrect answer explanations

A. X-linked dominant 

Incorrect: In X-linked dominant inheritance, at least one parent (of either sex) is affected.

C. Autosomal dominant 

Incorrect: In autosomal dominant inheritance, more than one generation is affected; therefore, at least one parent should also be affected. Both male and females can have the disease. 

D. Autosomal recessive 

Incorrect: Autosomal recessive conditions usually affect only one generation, and both parents of the affected child should at least be a carrier of the disease. With two carrier parents, only 25% of the children will be affected, and both males and females can be affected by the mutation. 

E. Mitochondrial 

Incorrect: Diseases that have mitochondrial inheritance are transmitted only by females, and all of the affected female’s offspring are likely to show the signs of the disease. 

Main Explanation

The pedigree shows that only males are affected by the disease. Specifically, male offspring of unaffected parents are affected and there is no evidence of male-to-male transmission. This pattern is most likely suggestive of X-linked recessive inheritance from an asymptomatic carrier female in the first generation. In X-linked recessive disease: 

• If the female is a carrier,  50% of her sons will end up having the mutation and 50% of daughters will be carriers for the mutation. 

• Affected males will always produce unaffected sons and carrier daughters. 

This patient is most likely suffering from Duchenne muscular dystrophy (DMD). About 2/3rds of the time, the affected patient’s mother is a carrier, and the other 1/3rd of the time the disease is sporadic, which means it is caused by a new mutation. Patients with DMD may experience a gradual and relentless deterioration, and most patients lose ambulation before the age of 12 years. Most patients with DMD die in their 20s or 30s. Therefore, it is important to counsel the parents regarding the risk of having another child with a similar mutation.   

Becker muscular dystrophy (BMD) is similar to DMD but manifests later in life. It is also an X-linked recessive disease. BMD patients typically have a milder clinical course than those with DMD, and remain ambulatory into adult life. They usually survive beyond the age of 30 years and have a mean age of death in the mid-40s. 

Major Takeaway

In diseases demonstrating an X-linked recessive inheritance, carrier females have 50% chance of producing affected sons and 50% chance of carrier daughters. Furthermore, affected males will always produce unaffected sons and carrier daughters, with no male-to-male transmission. Duchenne and Becker muscular dystrophies are inherited as X-linked recessive disorders. 

References

• "Muscular Dystrophy: Hope Through Research". NINDS. March 4, 2016. Archived from the original on 30 September 2016. Retrieved 12 September 2016. 

                                                         ________________________

Want more USMLE® Step 1 practice questions? Try Osmosis by Elsevier today! Access your free trial and find out why millions of current and future clinicians and caregivers love learning with us.

_{The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB.}