A 19-year-old man comes to the office to establish medical care. He is transitioning care from his pediatrician. The patient states that he recently changed his glasses for myopia; he otherwise has no symptoms. He takes no medications. Vital signs are within normal limits. On physical examination, the patient is tall with long upper extremities and fingers. The face appears narrow with down-slanted palpebral fissures, flattened malar bones, and a small jaw. The lungs are clear on auscultation. A late-systolic murmur is present at the cardiac apex. The abdomen is soft and nontender with no organomegaly. Which of the following is the most likely cause of this patient's murmur?

Question

A 19-year-old man comes to the office to establish medical care.  He is transitioning care from his pediatrician.  The patient states that he recently changed his glasses for myopia; he otherwise has no symptoms.  He takes no medications.  Vital signs are within normal limits.  On physical examination, the patient is tall with long upper extremities and fingers.  The face appears narrow with down-slanted palpebral fissures, flattened malar bones, and a small jaw.  The lungs are clear on auscultation.  A late-systolic murmur is present at the cardiac apex.  The abdomen is soft and nontender with no organomegaly.  Which of the following is the most likely cause of this patient's murmur?

Quizplus · Accepted Answer

This patient has clinical features of Marfan syndrome, an autosomal dominant disorder caused by mutations in the FBN1 gene encoding fibrillin-1, a main component of extracellular matrix microfibrils. Fibrillin-1 provides support to elastic fibers and helps maintain connective tissue integrity. It also regulates extracellular matrix remodelling by binding to and sequestering transforming growth factor-beta (TGF-beta). In Marfan syndrome, defective fibrillin-1 is unable to bind TGF-beta. The resulting overexpression of free, active TGF-beta leads to increased production of matrix metalloproteinases, which cleave elastic fibers and other components of the extracellular matrix, reducing tissue integrity. Within the mitral valve, this process results in fragmentation of elastic fibers and decreased collagen density with pooling of glycosaminoglycans (myxomatous mitral degeneration). The elongated, floppy mitral valve leaflets prolapse into the atrium, which causes a midsystolic click on auscultation and allows for mitral valve regurgitation. This regurgitant flow is characterized by a mid-to-late systolic apical murmur, as seen in this patient; severe regurgitation may produce a holosystolic murmur. (Choice A) Although aortic root dilation is common with Marfan syndrome, the associated aortic regurgitation causes a decrescendo diastolic murmur. (Choice B) Aortic valve cusp fusion (ie, bicuspid aortic valve) is commonly associated with Turner syndrome, not Marfan syndrome. Auscultatory findings are attributed to aortic stenosis (systolic crescendo-decrescendo murmur at the right upper sternal border) and/or aortic regurgitation (diastolic murmur along the left sternal border). (Choice C) Endocardial fibrous deposition occurs with carcinoid heart disease. In contrast to this case, presentation includes right-sided heart failure (eg, edema, hepatomegaly), and common murmurs include tricuspid regurgitation (ie, holosystolic murmur at the left lower sternal border) and pulmonic regurgitation (ie, diastolic decrescendo murmur). (Choice E) Papillary muscle dysfunction, which is typically the result of myocardial ischemia/infarction, can cause mitral regurgitation (ie, holosystolic murmur). Marfan syndrome is not associated with papillary muscle dysfunction. Educational objective: Marfan syndrome is a connective tissue disorder in which defective fibrillin-1 decreases tissue integrity and increases expression of transforming growth factor-beta. Cardiac effects include myxomatous degeneration and prolapse of the mitral valve with associated regurgitation, which manifests as a midsystolic click and mid-to-late systolic murmur.

A 19-Year-Old Man Comes to the Office to Establish Medical