Marfan Syndrome

Cardiology section

Marfan syndrome, a genetic disorder, affects the connective tissue throughout the body, which is responsible for providing strength and flexibility to various structures such as bones, ligaments, muscles, blood vessels, and heart valves. The manifestations of Marfan

syndrome exhibit wide variation in severity, onset timing, and progression rate. Given the widespread distribution of connective tissue, this syndrome can affect multiple bodily systems, resulting in abnormalities in the heart, blood vessels, eyes, bones, and joints.

About Marfan Syndrome

UNDERSTANDING MARFAN SYNDROME

Exploring Marfan Syndrome: Key Clinical Characteristics

The key features of Marfan syndrome include vision problems due to a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel responsible for distributing blood from the heart to the rest of the body, known as the aorta. The aorta may undergo weakening and stretching, potentially

leading to the formation of a bulge in the blood vessel wall (aneurysm). Such stretching can also cause the aortic valve to leak, increasing the risk of a sudden tear in the layers of the aorta wall (aortic dissection). Both aortic aneurysm and dissection pose life-threatening risks.

Marfan syndrome is primarily caused by mutations in the FBN1 gene, which provides instructions for making fibrillin-1, a protein that is essential for the formation of elastic fibers in connective tissue.

FBN1 (Fibrillin-1)

Mutations in the FBN1 gene are responsible for the majority of cases of Marfan syndrome. Fibrillin-1 is a major component of microfibrils in connective tissue, and it plays a crucial role in providing strength, flexibility, and support to various tissues, including the skeletal system, blood vessels, and heart valves. Mutations in FBN1 can lead to structural abnormalities in connective tissue, resulting in the characteristic features of Marfan syndrome, such as tall stature, long limbs, joint hypermobility, and cardiovascular complications like aortic aneurysms and mitral valve prolapse.

Mutations in other genes (TGFBR1, TGFBR2)

In rare cases, Marfan syndrome can be caused by mutations in other genes, including TGFBR1 (encoding a receptor for transforming growth factor-beta) and TGFBR2 (encoding another receptor for transforming growth factor-beta), which are involved in the TGF-beta signaling pathway. Additionally, mutations in genes such as SMAD3 (encoding a protein that transduces TGF-beta signals) and TGFB2 (encoding transforming growth factor-beta 2) have also been implicated in some cases of Marfan syndrome, although these are less common than FBN1 mutations.

Marfan syndrome follows an autosomal dominant inheritance pattern, meaning that a person only needs to inherit one copy of the mutated gene from one parent to develop the condition.

As a result, individuals with Marfan syndrome have a 50% chance of passing the mutated gene to each of their children. Genetic testing can help confirm a diagnosis of Marfan syndrome by identifying mutations in the FBN1 gene or other associated genes. However, clinical diagnosis typically involves a combination of physical examination, family history assessment, and evaluation of characteristic features and manifestations of the condition, such as skeletal abnormalities, ocular findings (such as lens dislocation), and cardiovascular complications.