Medical Mystery of the Week

       You are asked to make a diagnosis in this 24-year-old man based on his picture and a recording of his heart sounds.
      DIAGNOSIS: Marfan syndrome (MFS).
      MFS is a multisystem connective tissue disorder with a global prevalence of one in 3,000 to 5,000. The primary genetic defect in MFS lies on chromosome 15q21.1 within the coding region of the fibrillin-1 (FBN1) gene. FBN1 is a large glycoprotein produced by tissue fibroblasts which is secreted into the extracellular matrix as insoluble microfibrils. These microfibrils serve as a scaffold for the deposition of elastin and for the sequestration of transforming growth factor (TGF)ß which prevents overstimulation of the TNFß pathway.
      The most important clinical manifestations of MFS are cardiovascular, particularly aortic aneurysms (thoracic and abdominal). The thoracic aneurysms are unique in that the ascending aorta and arch may retain their normal dimensions leading to an "Erlenmeyer flask" shaped aneurysm originating at the the aortic valve annulus; these aneurysms are prone to dissection and rupture, the leading causes of death in patients with MFS. Other MFS manifestations may include mitral and tricuspid valve prolapses, cardiomyopathy, scoliosis, pectus deformities, joint laxity, arachnodactyl, increased arm span, enophthalamos, hypertelorism, ectopia lentis, dural ectasia, spontaneous pneumothorax, and striae atrophicae.
      The diagnosis of MFS is based on clinical findings, family history, and genetic testing. Patients with MFS should have biannual echocardiograms to assess the size of the aortic root and the integrity of the tricuspid and mitral valves. Patients should avoid high impact and isometric exercises and should not participate in competitive sports. The role of beta blocker therapy is unresolved.

 The patient has arachnodactyl and some joint laxity (left image). The recording shows both diastolic and systolic clicks and a midsystolic murmur all characteristic of MVP (right image).     

Reference: Zeigler S, Sloan  B, Jones JA. The pathophysiology and pathogenesis of Marfan syndrome. Adv Exp Med Biol. 2021; 1348:185-206.