Pathophysiology and Japanese clinical characteristics in Marfan syndrome

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Medicine
• Rheumatology

Background:

• Marfan syndrome is an autosomal dominant disorder caused by FBN1 gene mutations, affecting fibrillin-1 and extracellular matrix.
• Dysregulated transforming growth factor-β (TGF-β) signaling is implicated in Marfan syndrome pathogenesis, particularly in aortic aneurysm and dissection.
• Current diagnostic criteria (Ghent nosology) can be complex and time-consuming for single physicians to evaluate.

Purpose of the Study:

• To review recent advancements in the diagnosis and treatment of Marfan syndrome.
• To discuss the potential of Losartan, an angiotensin II blocker, in managing TGF-β signaling in Marfan syndrome.
• To highlight the characteristics of Japanese patients with Marfan syndrome and the establishment of a multidisciplinary Marfan clinic.

Main Methods:

• Review of current literature on Marfan syndrome diagnosis and treatment.
• Discussion of the role of FBN1 gene, fibrillin-1, and TGF-β signaling pathways.
• Description of the multidisciplinary approach in a specialized Marfan clinic.

Main Results:

• Fibrillin-1 mutations disrupt extracellular matrix and TGF-β signaling, contributing to Marfan syndrome.
• Losartan demonstrates potential therapeutic benefits by modulating TGF-β signaling.
• A dedicated Marfan clinic facilitates efficient and accurate diagnosis and patient management.

Conclusions:

• Marfan syndrome requires comprehensive management due to its systemic connective tissue involvement.
• Targeting TGF-β signaling with agents like Losartan offers a promising therapeutic avenue.
• Multidisciplinary clinics are crucial for optimizing the diagnosis and care of Marfan syndrome patients, including specific considerations for Japanese populations.