What is Marfan's syndrome?

From the Guidelines

Patients with Marfan syndrome should be treated with either a beta blocker or an angiotensin receptor blocker (ARB) in maximally tolerated doses to reduce the rate of aortic dilation, as recommended by the 2022 ACC/AHA guideline for the diagnosis and management of aortic disease 1. Marfan syndrome is a genetic disorder that affects the body's connective tissue, which provides strength and flexibility to structures throughout the body. It is caused by mutations in the FBN1 gene, which provides instructions for making fibrillin-1, a protein essential for forming elastic fibers in connective tissue. People with Marfan syndrome typically have tall, slender builds with disproportionately long arms, legs, and fingers. The most serious complications involve the heart and blood vessels, particularly enlargement of the aorta, which can lead to life-threatening aortic dissection or rupture.

Key Features and Management

• The most serious complications involve the heart and blood vessels, particularly enlargement of the aorta, which can lead to life-threatening aortic dissection or rupture.
• Other common features include lens dislocation in the eyes, a curved spine (scoliosis), chest wall deformities, and flat feet.
• Management includes regular cardiac imaging to monitor aorta size, medications like beta-blockers (such as atenolol or propranolol) or angiotensin receptor blockers (like losartan) to reduce stress on the aorta, and sometimes prophylactic surgery if the aorta becomes too enlarged.
• Physical activity restrictions may be necessary, particularly avoiding contact sports and isometric exercises.
• Genetic counseling is important for affected individuals and their families, as Marfan syndrome follows an autosomal dominant inheritance pattern, meaning each child of an affected parent has a 50% chance of inheriting the condition. According to the 2022 ACC/AHA guideline, beta blockers have long been recommended for patients with Marfan syndrome to reduce heart rate and myocardial contractility and to slow aortic root growth, and more recently, ARBs have also been found to be efficacious in Marfan syndrome 1.

Medical Therapy

• The use of both a beta blocker and an ARB, in maximally tolerated doses, is reasonable to reduce the rate of aortic dilation in patients with Marfan syndrome 1.
• The rate of aortic dilation is faster in patients with larger aortic aneurysms, and more frequent imaging is performed in patients with rapid aortic growth, in those approaching surgical thresholds, or when the diameter exceeds 4.5 cm 1.

From the Research

Marfan Syndrome Overview

• Marfan syndrome (MFS) is an autosomal dominant, age-related condition with substantial intrafamilial and interfamilial variability 2
• MFS is caused by pathogenetic variants in FBN1, which encodes fibrillin-1, a major structural component of the extracellular matrix 2
• The most prominent manifestations of MFS are asymptomatic aortic root aneurysms, aortic dissections, dislocation of the ocular lens (ectopia lentis), and skeletal abnormalities 2

Treatment and Management

• Management of MFS requires medical therapy to slow the rate of growth of aneurysms and decrease the risk of dissection 2
• β-blockers remain the standard of preventive treatment for MFS 3, 4
• Losartan, an angiotensin II receptor blocker, has been studied as a potential treatment for MFS, with some studies showing benefit in reducing aortic root dilation 3, 5, 6
• However, a large-scale study found that losartan did not limit aortic dilatation during a 3-year period in patients >10 years old 4

Losartan Therapy

• Losartan has been shown to decrease blood pressure in patients with MFS, but its effect on aortic root dilation is still unclear 4, 6
• Some studies suggest that losartan's antiremodeling properties may be angiotensin II receptor type 1 (ATR1) independent, and that endothelial function activation may be of therapeutic significance in preventing aortic root disease in MFS 6
• Further research is needed to fully understand the role of losartan in the treatment of MFS 3, 6

Diagnosis and Surveillance

• MFS is diagnosed based on the Ghent II nosology, and genetic testing confirming the presence of a FBN1 pathogenetic variant can help distinguish MFS from other heritable thoracic aortic disease syndromes 2
• Routine surveillance with imaging techniques such as transthoracic echocardiography, CT, or MRI is necessary to monitor aneurysm growth and determine when to perform prophylactic repair surgery to prevent an acute aortic dissection 2