WBR0120

Author	[[PageAuthor::William J Gibson (reviewed by Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Cardiology
Prompt	[[Prompt::An 18-year-old male collapses while playing in a basketball game. Despite CPR, he dies before ambulances arrives. Distraught, the parents order an autopsy. Toxicological screening is negative for alcohol or illicit drugs. The pathologist notes a large, thick myocardium with disarrayed muscle fibers on autopsy. The pathologist concludes that the left ventricular septum “bulged” outward into the left ventricular outflow tract, obstructing blood flow out of the heart and causing a myocardial ischemia. The patient likely died of an arrhythmia following said ischemia. Which of the following most likely describes the inheritance of the patient’s condition?]]
Answer A	AnswerA::Mutation in sarcomere; autosomal dominant
Answer A Explanation	[[AnswerAExp::Hypertrophic obstructive cardiomyopathy (HOCM) is caused by mutation of sarcomere proteins and is inherited in an autosomal dominant fashion.]]
Answer B	AnswerB::Mutation in sarcomere; autosomal recessive
Answer B Explanation	AnswerBExp::HOCM is inherited in an autosomal dominant fashion.
Answer C	AnswerC::Mutation in calcium channel; autosomal dominant
Answer C Explanation	AnswerCExp::HOCM is not caused by mutations in the calcium channels. However, HOCM can be treated with a calcium channel blocker to decrease myocardial contractility.
Answer D	[[AnswerD::Mutation in ryanodine receptor; autosomal recessive]]
Answer D Explanation	AnswerDExp::HOCM is not caused by mutations in the ryanodine receptor.
Answer E	AnswerE::Mutation in myostatin; autosomal dominant
Answer E Explanation	[[AnswerEExp::Mutations of myostatin are extremely rare and cause widespread, gross muscle hypertrophy.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::The patient in this vignette suffered from hypertrophic cardiomyopathy, sometimes called Hypertrophic Obstructive Cardiomyopathy (HOCM). HOCM is most commonly due to a mutation in one of 9 sarcomeric genes that results in a mutated protein in the sarcomere, the primary component of the myocyte (the muscle cell of the heart). It is inherited in an autosomal dominant pattern. Educational Objective: Hypertrophic cardiomyopathy is caused by mutation of sarcomere proteins and is inherited in an autosomal dominant fashion. References: First Aid 2014 page 290; First Aid 2012 page 299]]
Approved	Approved::Yes
Keyword	WBRKeyword::HOCM, WBRKeyword::Hypertrophic cardiomyopathy, WBRKeyword::HCM, WBRKeyword::Genetics, WBRKeyword::Sudden death
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::