Marfan Syndrome: A Clinical Update

Adam D. Bitterman, DO; Paul D. Sponseller, MD, MBA


J Am Acad Orthop Surg. 2017;25(9):603-609. 

In This Article

Abstract and Introduction


Marfan syndrome is a connective tissue disorder that can affect many organ systems. Affected patients present with orthopaedic manifestations of the syndrome during all phases of life. Pain caused by musculoskeletal abnormalities often requires definitive orthopaedic treatment. Orthopaedic surgeons must understand the phenotypes of Marfan syndrome so they can recognize when screening is warranted and can appropriately address the skeletal manifestations. Through medical advancements, patients with Marfan syndrome are living longer and more active lives. Knowledge of the latest diagnostic criteria for the disorder, as well as of advances in understanding the skeletal phenotype, clinical trials of medication therapy, and lifestyle considerations is important for orthopaedic surgeons who treat these patients because these clinicians often are the first to suspect Marfan syndrome and recommend screening.


Marfan syndrome (MFS) is an autosomal dominant disorder best known for its associated cardiovascular abnormalities. It is now understood to affect many other systems, including the ophthalmologic and pulmonary systems. Musculoskeletal symptoms include generalized ligamentous laxity, scoliosis, chest deformity, protrusio acetabuli, foot deformities, hypermobility, dural ectasia, and low bone mineral density.

The protein encoding fibrillin-1, known as the FBN1 gene, is located on chromosome 15.[1] Fibrillin-1 is the main component of elastic matrix microfibrils, which have a role in the connective tissue of the cardiovascular and musculoskeletal systems. Although cardiovascular manifestations are the main cause of death in patients with MFS, medical therapies combined with early surgical management, serial cardiac imaging, refined exercise participation, and strict blood pressure control have improved overall survival.[2]

The initial suspicion of the role of transforming growth factor-beta (TGF-β) in MFS is now confirmed.[3] Studies of mice showed that fibrillin-1 deficiency leads to an increase in TGF-β, and the excessive signaling and activation of TGF-β are theorized to cause the various manifestations of MFS.[4,5]

Advanced medical and surgical therapies for aortic dilatation allow patients with MFS to live longer. Life expectancy has increased from 47 years to 75 years.[6] Furthermore, aortic measurement surveillance through echocardiography has allowed cardiologists to better tailor treatment with angiotensin-receptor blockers and β-blockers. Surgical interventions continue to evolve and include valve-sparing and composite graft replacement techniques. Cardiac surgeons are seeing musculoskeletal manifestations of the disease, which require the attention of orthopaedic surgeons.