Marfan Syndrome: Recognition, Diagnosis and Managements

Dear Colleagues,

Marfan syndrome is one of the most common single gene abnormalities. First described by Antoine Marfan 118 years ago, the syndrome has shown remarkable pleiotropisms because it is being recognized more widely in “asymptomatic” individuals. Seventy to eighty percent of affected individuals develop aortic root dilatation and somewhat fewer patients develop mitral and aortic valve abnormalities, which account for the gravest manifestations of this connective tissue disease. In addition to the commonly found skeletal manifestations, dural ectasia is reported in > 90% of patients on MRI and CT scan studies.

After nearly 80 years since the initial diagnosis of the syndrome, on somewhat inconsistent phenotypic criteria, a consensus document, the Berlin nosology, attempted to standardize the phenotypic diagnosis. A more recent and more detailed revision, the Ghent Criteria in 1996, facilitated a more specific and sensitive phenotypic diagnosis of Marfan syndrome; the criteria include available genetic data. Microfibrills have been thought to contribute to the structural integrity of connective tissue. In the late 1980s, quantitative elastin-associated microfibrillar analysis of skin fibroblasts via indirect immunoflourescence staining pointed to a deficiency of the glycoprotein, fibrillin, as the possible cause of Marfan syndrome.

More recently, it has been demonstrated that normal fibrillin-1 contributes to cell signaling activity by binding to the protein transforming growth factor beta (TGF-β).

Abnormal TGF-β regulation and gene expression have deleterious effects on arterial wall development as well as on extracellular matrix formation. It has been demonstrated that abnormal as well as deficient fibrillin and excessive TGF-β levels weakens cardiovascular tissues and causes the features of Marfan syndrome. It has been demonstrated that angiotensin II receptor antagonists (ARBs) also reduce TGF-β, ARBs (e.g., losartan) in the animal lab, and reduced and even reversed (in some cases) aortic root dilatation. Losartan is being evaluated in a small study of pediatric Marfan syndrome patients. The results will be available in the near future.

Survival with Marfan syndrome improved from a life expectancy of around 45–50 years to over 70 years (in the 1970’s). This progress has been achieved through improved clinical, and more recently, genetic diagnostics. With a better understanding of the mechanisms of Marfan syndrome, there may be more effective, targeted therapies available in the near future. At the same time, earlier diagnoses and better surgical techniques have lead to better surgical outcomes and improved survival rates.

This Special Issue provides an Open Access opportunity to publish research and review articles concerning Marfan syndrome, its diagnosis, and treatment. The emphasis will be on a comprehensive review of the current literature, as well as on insights into the improvement of clinical and genetic diagnoses, medical and surgical management, and targeted therapy.

Dr. Peter Varga
Guest Editor

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• marfan syndrome
• thoracic aortic aneurysms
• surgical repair of ascending aortic aneurysm
• medical therapy in marfan syndrome
• TGF BR1 and TGF BR2 mutation
• TGFB receptor targeted therapy
• ectopia lentis
• dural ectasia
• loeys-Dietz syndrome