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Diving deeper into Orphan Diseases - Marfan Syndrome - Part 1

The next orphan disease we want to focus on is the Marfan syndrome (MFS).  

Disclaimer: Since we just touch on some facts in this article, more in-depth information and contacts for affected patients can be found here:


Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the FBN1 gene, which codes for fibrillin-1, an important protein in the connective tissue.  MFS can result in a diverse range of symptoms with cardiovascular, musculoskeletal, ophthalmic and pulmonary features, that can vary widely in its clinical presentation, ranging from mild forms affecting only a few organ systems to severe, rapidly progressing multi-organ disease, especially in newborns. The prevalence is approximately 1 in 5,000, and it does not vary between genders.  


But what is MFS? 

MFS is caused by mutations in the FBN1 gene, located on chromosome 15, which encodes the fibrillin-1 protein. The pathogenesis of Marfan syndrome is primarily attributed to these genetic mutations in the FBN1 gene.  Fibrillin-1 is a crucial component of microfibrils in the extracellular matrix, which are found in various tissues, including elastic and non-elastic tissues. These microfibrils play a crucial role in maintaining the elastic matrix, facilitating cell-to-matrix interactions, and regulating the activity of growth factors. The exact mechanisms by which abnormal or deficient fibrillin-1 lead to the Marfan syndrome phenotype and related disorders are not fully understood. 

The abnormal fibrillin-1 resulting from these mutations leads to several key mechanisms,  which have an especially fatal outcome in the cardiovascular pathology in MFS. Abnormal fibrillin leads to increased levels of activated transforming growth factor beta (TGF-ß), a cytokine regulation tissue repair, causing elevated collagen deposition and elastin degradation within the arterial wall's elastic media. Elastic fiber fragmentation, loss of elastin content, and the accumulation of amorphous matrix components are found in the aortic media. This results in stiffening of the artery, leading to an increase in its diameter of the vessel forming an aneurysm, most commonly forming at the aortic root (see figure). 


As the artery's diameter enlarges, the risk of arterial dissection rises. Aortic dissection occurs when there is a tear in the aorta's wall, allowing blood to flow between the layers of the aortic wall. The enlarged aorta is at an increased risk of arterial dissection, a condition where a tear occurs in the aortic wall, allowing blood to flow between the layers of the aortic wall. This can reduce blood supply to distal organs and may lead to catastrophic consequences. If left untreated, dissection can result in complete rupture, often involving the aortic root in MFS, leading to sudden and potentially fatal outcomes.

What are symptoms of MFS? 

MFS can present with a variety of symptoms, and the severity and combination of these can vary from patient to patient. Characteristics of MFS include:

  • Cardiovascular issues manifested in aneurysm formation muskosceletal abnormalities

  • Common eye issues include ectopia lentis, myopia, glaucoma risk, premature cataracts, and retinal detachment

  • Skeletal effects involve joint laxity, excessive limb length relative to the trunk, pectus excavatum or carinatum, and scoliosis

Cardiovascular complications, especially aortic problems and valve issues can lead to serious health risks such as the formation of aneurysms with a high risk of aortic dissection. Proper management can result in a similar lifespan to the general population, but fatal aortic dissections can still occur.

How is MFS inherited and diagnosed? Stay tuned for part 2 and sign up and stay informed with everything that´s happening at Elastrin Therapeutics:



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