Snapshot A 32-year-old man presents to the emergency room for sudden onset of severe chest pain that radiates down his back. Physical exam reveals a tall and thin habitus, arachnodactyly, and pectus excavatum. Radiography shows widened mediastinum, concerning for an aortic dissection. Introduction Clinical definition inherited connective tissue disorder characterized by aortic abnormalities and musculoskeletal deformities Epidemiology Demographics clinical manifestations typically occur in adulthood Etiology Pathogenesis fibrillins form a major part of connective tissues and provide structural support and elasticity to blood vessels, skin, and bones abnormalities in fibrillin can result in aortic abnormalities (cystic medial necrosis) ectopic lens (structural weakness in ligaments of the lens) skeletal deformities Genetics inheritance pattern autosomal dominant mutations FBN1 gene is on chromosome 15 and encodes fibrillin-1, a glycoprotein that forms a protective sheath around elastin elastin is found in multiple parts of the body, including large arteries, skin, lungs, and ligaments Presentation Symptoms aortic dilation, aneurysm, or dissection dissection will present as acute severe retrosternal chest pain radiating to the back pneumothorax Physical exam skeletal tall and thin stature long extremities arm span exceeds height long fingers and toes (arachnodactyly) thumbnail protrudes beyond ulnar border of hand when crossed (thumb sign) thumb and little finger can encircle wrist (wrist sign) pectus carinatum or excavatum scoliosis hypermobile joints ocular subluxation of lenses (superior and temporal) cardiovascular mitral valve prolapse mid-systolic click followed by a late systolic murmur aortic regurgitation diastolic murmur mitral regurgitation high-pitched holosystolic murmur Imaging Transthoracic echocardiography indication for all patients to evaluate for cardiac involvement findings mitral or aortic valve abnormalities aortic aneurysm or dissection Studies Making the diagnosis based on clinical presentation genetic testing is not always necessary but is diagnostic Differential Homocystinuria distinguishing factor lens subluxation is downwards mental retardation Ehlers-Danlos syndrome distinguishing factor hyperextensible skin and easy bruising middle-sized artery aneurysms > aortic aneurysms Treatment Management approach no curative treatment exists, so treatment is targeted at symptoms Conservative avoid high-impact contact sports indication for all patients Medical β-blockers or angiotensin receptor blockers indications to halt the progression of aortic root dilation Operative aortic aneurysm repair indication patients with aneurysms ≥ 4-4.5 cm cardiac valve repair indications patients with severe mitral or aortic valve disease Complications Aortic dissection most common cause of death Mitral valve prolapse Congestive heart failure from cardiac valve abnormalities Prognosis Survival has improved with better management of aortic disease With early diagnosis and management, patients often have a normal life expectancy