From the Guidelines
Marfan syndrome is a genetic disorder that affects the connective tissue in the body, causing problems in the skeletal, ocular, pulmonary, cutaneous, nervous, and cardiovascular systems.
Key Features of Marfan Syndrome
- Autosomal dominant inheritance: Marfan syndrome is caused by pathogenic variants in the FBN1 gene, affecting 1 in 5,000 individuals 1.
- Cardiovascular problems: Patients with Marfan syndrome are at risk of developing aneurysms involving the aortic root and are prone to aortic dissection, with aortic root dilation and type A aortic dissection being the leading causes of morbidity and mortality 1.
- Skeletal and ocular manifestations: Marfan syndrome is characterized by skeletal features such as arachnodactyly, dolichostenomelia, and kyphoscoliosis, as well as ocular manifestations like ectopia lentis or lens dislocation 1.
- Diagnosis and management: The modified Ghent criteria for diagnosis incorporate genetic testing, the systemic score, ectopia lentis, and family history, and patients with Marfan syndrome require regular imaging surveillance of the aorta, typically performed annually, with the frequency dependent on age, aortic diameter, rate of aortic growth, and family history 1.
Important Considerations
- Aortic root dilation: The aortic root and ascending aorta are measured by transthoracic echocardiography (TTE) and are observed annually, with nomograms accounting for age, sex, and body size assisting in determining the degree to which the diameter deviates from normal in the general population 1.
- Treatment and prevention: Prophylactic aortic root replacement for aneurysm disease prevents type A dissection and improves survival in Marfan syndrome, and beta blockers or angiotensin receptor blockers (ARBs) may be used to slow aortic root growth and reduce the risk of aortic dissection 1.
From the Research
Definition and Overview of Marfan Syndrome
- Marfan syndrome (MFS) is an autosomal dominant heritable disorder of fibrillin-1 (FBN1) with predominantly ocular, cardiovascular, and musculoskeletal manifestations 2, 3, 4, 5, 6.
- It is caused by pathogenetic variants in FBN1, which encodes fibrillin-1, a major structural component of the extracellular matrix that provides support to connective tissues 3, 5.
Clinical Manifestations
- The most prominent manifestations of MFS are asymptomatic aortic root aneurysms, aortic dissections, dislocation of the ocular lens (ectopia lentis), and skeletal abnormalities characterized by overgrowth of the long bones 3.
- MFS can also have musculoskeletal manifestations, such as joint hypermobility and scoliosis, which can have a significant impact on the quality of life 2.
- Cardiovascular complications, including mitral valve prolapse, aortic insufficiency, dilatation of the aortic root, and aortic dissection, are the most life-threatening manifestations of MFS 4, 5.
Diagnosis and Management
- MFS is diagnosed based on the Ghent II nosology, which requires a comprehensive clinical assessment of multiple organ systems 3, 5.
- Genetic testing confirming the presence of a FBN1 pathogenetic variant can help distinguish MFS from other heritable thoracic aortic disease syndromes 3, 5.
- Management of MFS requires medical therapy to slow the rate of growth of aneurysms and decrease the risk of dissection, as well as routine surveillance with imaging techniques to monitor aneurysm growth and determine when to perform prophylactic repair surgery 3.