Snapshot A 30-year-old man with a marfanoid habitus presents for genetic counseling. His father, paternal uncle, and paternal great-grandfather died of sudden cardiac deaths. His father, specifically, suffered from an aortic dissection. As part of this patient's work-up, he recently had cardiac imaging, which reveals a 5 cm aortic aneurysm. He is sent for further surgical consultation and is tested for suspected Marfan syndrome. Overview Introduction Clinical definition inherited connective tissue disorder characterized by aortic abnormalities and musculoskeletal deformities Epidemiology demographics clinical manifestations typically occur in adulthood 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 login to view 1 more bullet Prognosis survival has improved with better management of aortic disease with early diagnosis and management, patients often have a normal life expectancy Presentation Physical exam skeletal tall and thin stature long extremities login to view 1 more bullet long fingers and toes (arachnodactyly) login to view 2 more bullets pectus carinatum or excavatum scoliosis hypermobile joints ocular subluxation of lenses (superior and temporal) cardiovascular mitral valve prolapse login to view 1 more bullet aortic regurgitation login to view 1 more bullet mitral regurgitation login to view 1 more bullet 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 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 login to view 1 more bullet Medical β-blockers or angiotensin receptor blockers indications login to view 1 more bullet Operative aortic aneurysm repair indication login to view 1 more bullet Complications Aortic dissection most common cause of death Congestive heart failure from cardiac valve abnormalities