A 21-year-old man comes to the office due to multiple episodes of syncope. The patient has no chest discomfort or dyspnea. He has no known medical problems and does not use tobacco, alcohol, or illicit drugs. The patient is a computer analyst and leads a mostly sedentary lifestyle. He reports that several family members have died of sudden cardiac death. Genetic analysis reveals an ion channel defect. Due to the defect, cardiac cells show decreased outward potassium flow and resultant prolongation of the action potential. Which of the following is the most likely consequence of this patient's disease?

Question

A 21-year-old man comes to the office due to multiple episodes of syncope.  The patient has no chest discomfort or dyspnea.  He has no known medical problems and does not use tobacco, alcohol, or illicit drugs.  The patient is a computer analyst and leads a mostly sedentary lifestyle.  He reports that several family members have died of sudden cardiac death.  Genetic analysis reveals an ion channel defect.  Due to the defect, cardiac cells show decreased outward potassium flow and resultant prolongation of the action potential.  Which of the following is the most likely consequence of this patient's disease?

Quizplus · Accepted Answer

11ec160b_38d4_bc70_9249_61470ac72987_MD0001_00 This patient's recurrent syncope, family history of sudden death, and ion channel defect (decreased outward potassium flow with prolonged action potential) is suggestive of congenital long QT syndrome (LQTS). There are several genetic mutations described in patients with congenital LQTS. The 2 most common forms (LQT type 1 and LQT type 2) are due to genetic mutations in K+ channel proteins that contribute to the outward-rectifying potassium current. Phase 3 (repolarization) of the myocardial action potential occurs due to time-dependent inactivation of the L-type (long-lasting, large-conductance) Ca²⁺ channels (which reduces inward current) along with activation of the voltage-gated delayed rectifier K⁺ channels (which increases outward current). This net increase in outward transmembrane current is responsible for ventricular repolarization. Decreased outward potassium flow due to K⁺ channel mutations leads to prolongation of action potential duration and QT interval. Prolongation of QT interval predisposes to the development of life-threatening ventricular arrhythmias (eg, torsades de pointes), which can present as recurrent palpitations, syncope, seizures, or sudden cardiac death. (Choice A) Abnormal anatomic communication between cardiac chambers presents in patients with atrial septal defects, ventricular septal defects, or patent ductus arteriosus. These disorders are not associated with any genetic defects in ion channels. (Choice B) Asymmetric hypertrophy of the left ventricle occurs in patients with hypertrophic cardiomyopathy, an autosomal dominant disorder caused by mutations in sarcomere genes. The 2 most common mutations involve the cardiac myosin-binding protein C gene and cardiac beta-myosin heavy chain gene. (Choice C) Ischemic myocardial necrosis and scarring occur in myocardial infarction and often lead to left ventricular systolic dysfunction. Patients with scarred myocardium are also at increased risk for developing ventricular arrhythmias; however, these arrhythmias would not be associated with an ion channel defect. (Choice D) Dilated cardiomyopathy is characterized by left ventricle dilation and systolic dysfunction. Several genetic mutations involving the sarcomere structure and function have been identified in patients with familial dilated cardiomyopathy. However, abnormal transmembrane K⁺ currents are not known to be directly involved in the pathophysiology. Educational objective: Congenital long QT syndrome is most often caused by genetic mutations in a K⁺ channel protein that contributes to the outward-rectifying potassium current. A decrease in the outward K⁺ current leads to prolongation of action potential duration and QT interval. This prolongation predisposes to the development of life-threatening ventricular arrhythmias (eg, torsades de pointes) that can cause palpitations, syncope, seizures, or sudden cardiac death.

A 21-Year-Old Man Comes to the Office Due to Multiple