What is Marfan syndrome?

From the Guidelines

Marfan syndrome is a genetic disorder affecting connective tissue throughout the body, primarily caused by mutations in the FBN1 gene which produces fibrillin-1 protein, and its management requires a multidisciplinary approach focusing on cardiovascular monitoring and treatment to reduce morbidity, mortality, and improve quality of life. The disorder is characterized by its effects on the cardiovascular, ocular, and skeletal systems, with patients being highly predisposed to thoracic aortic aneurysm and/or dissection 1.

Key Features and Management

• The cardinal features of Marfan syndrome involve the cardiovascular, ocular, and skeletal systems, with aortic root dilation and type A aortic dissection being the leading causes of morbidity and mortality 1.
• Management includes the use of beta-blockers like metoprolol (25-200 mg daily) or atenolol (25-100 mg daily) to reduce stress on the aorta by lowering blood pressure and heart rate, as well as angiotensin receptor blockers (ARBs) such as losartan (50-100 mg daily) which may help slow aortic root enlargement 1.
• Regular cardiac imaging with echocardiograms is essential, typically every 6-12 months depending on aortic dimensions, to monitor the progression of aortic disease 1.
• Prophylactic aortic root surgery is recommended when the aortic root diameter reaches 4.5-5.0 cm or shows rapid growth (>0.5 cm/year), as this prevents type A dissection and improves survival in Marfan syndrome patients 1.
• Physical activity restrictions, annual eye examinations for lens dislocation and other ocular complications, and orthopedic intervention for skeletal manifestations like scoliosis are also crucial components of management 1.
• Genetic counseling is important for family planning, given Marfan syndrome's autosomal dominant inheritance pattern, meaning affected individuals have a 50% chance of passing the condition to each child 1.

Recent Guidelines and Recommendations

The 2022 ACC/AHA guideline for the diagnosis and management of aortic disease emphasizes the importance of prophylactic aortic root replacement for aneurysm disease in preventing type A aortic dissection and improving survival in Marfan syndrome 1. The guideline provides specific recommendations for the size threshold for elective surgery to replace the dilated aortic root, considering factors such as patient age, height, weight, family history, rate of aortic growth, and other patient-specific factors 1.

Conclusion is not needed as per the guidelines, the above information is sufficient to understand Marfan syndrome and its management.

From the Research

Definition and Characteristics of Marfan Syndrome

• Marfan syndrome is a genetic disorder of connective tissue with principal manifestations in the cardiovascular, ocular, and skeletal systems 2.
• It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural, and pulmonary systems 3.
• Aortic root dilatation is the most frequent cardiovascular manifestation, and its complications, including aortic regurgitation, dissection, and rupture, are the main cause of morbidity and mortality 3.

Medical Therapy for Marfan Syndrome

• Medical therapy for Marfan syndrome should be individualized according to patient tolerance and risk factors such as age, aortic size, and family history of aortic dissection 2.
• Beta-blockers are the standard treatment in Marfan syndrome (MFS) 4.
• Losartan has been proposed as a new therapeutic tool for preventing aortic growth and ventricular dysfunction in patients with Marfan syndrome 5.
• The combination of losartan and beta-blocker therapy may be considered for patients with severe and/or progressive aortic dilation, although trial results are mixed with respect to the efficacy of combination therapy vs monotherapy 2.

Treatment Outcomes and Efficacy

• The Pediatric Heart Network trial showed that atenolol and losartan each reduced the rate of aortic dilation 2.
• Long-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups 4.
• Beta-blocker therapy did not reduce the incidence of all-cause mortality, aortic dissection, aortic regurgitation, congestive heart failure, or cardiovascular surgery in patients with Marfan syndrome 3.
• Losartan on top of beta-blocker therapy has no additional effect on aortic growth or on cardiac function in patients with Marfan syndrome 5.