Marfan Syndrome - causes, symptoms, diagnosis, treatment, pathology

Summary

Marfan syndrome, an autosomal dominant genetic disorder, results from mutations in the FBN1 gene. This leads to defective fibrillin-1, affecting connective tissue integrity and elasticity. Symptoms include tall stature, elongated limbs, and cardiovascular issues, with aortic dilation being a major concern. Treatments focus on managing clinical features and slowing disease progression.

Takeaways

• 🧬 Marfan syndrome is a genetic disorder affecting connective tissue due to mutations in the FBN1 gene.
• 🌟 The primary component of microfibrils, fibrillin, is crucial for tissue integrity and elasticity.
• 🔍 Fibrillin also regulates tissue growth by sequestering TGF-β, reducing its availability to stimulate growth.
• 🧬 FBN1 gene mutations lead to dysfunctional or less abundant fibrillin-1, impacting the extracellular matrix.
• 🦴 Marfan syndrome affects the skeleton, causing excessive growth in long bones and a Marfanoid body habitus.
• 🕷️ Arachnodactyly refers to the long, thin fingers and toes associated with Marfan syndrome.
• 🔍 Other skeletal effects include scoliosis, joint flexibility, and dental crowding due to a narrow palate.
• 🫁 Pulmonary complications can include stretch marks on the skin and bullae in the lungs, which can lead to pneumothorax.
• 👀 Ocular issues such as retinal detachment and lens dislocation are common in Marfan syndrome.
• ❤️ Cardiovascular complications are the most serious, including aortic dilation, cystic medial necrosis, and risks of aneurysm and dissection.
• 🛠️ While there is no cure, treatments can manage clinical features, such as surgical repair of the aorta and medication to slow aortic dilation.

Q & A

What is Marfan syndrome?

Marfan syndrome is a genetic disorder that affects the connective tissue, impacting the skeleton, heart, blood vessels, eyes, and lungs. It is caused by mutations in the FBN1 gene, which encodes the fibrillin-1 protein.

What role do microfibrils play in the body?

Microfibrils are strong, ropelike structures that provide tissue integrity and form connective tissue. They are composed mainly of a glycoprotein called fibrillin and also serve as a scaffold for additional proteins like elastin.

How do elastin fibers contribute to tissue function?

Elastin fibers are highly cross-linked, giving them a rubber-band-like quality. This allows tissues to stretch and then return to their original shape, which is crucial for tissues like arteries, skin, and lungs.

What is the function of fibrillin in tissue growth regulation?

Fibrillin regulates tissue growth by sequestering or removing transforming growth factor beta (TGF-β), which stimulates tissue growth. By lowering the availability of TGF-β, fibrillin helps control tissue growth.

How does Marfan syndrome affect the skeletal system?

Marfan syndrome leads to excessive growth of long bones, resulting in a tall stature with long arms and legs (Marfanoid body habitus), long, thin fingers and toes (arachnodactyly), and overgrowth of ribs causing chest deformities like pectus excavatum or pectus carinatum.

What are the cardiovascular implications of Marfan syndrome?

Marfan syndrome can cause the aorta to dilate, leading to aortic valve insufficiency, cystic medial necrosis, and an increased risk of aortic aneurysm, dissection, and rupture. It is also a risk factor for mitral valve prolapse.

How does Marfan syndrome affect the eyes?

Marfan syndrome increases the risk of retinal detachment and lens dislocation, typically in an upward direction, which can lead to vision problems.

What are some of the skin and lung manifestations of Marfan syndrome?

In the skin, Marfan syndrome can cause stretch marks, and in the lungs, it can lead to the formation of bullae, large spaces that replace normal lung architecture and can cause pneumothorax.

How is Marfan syndrome diagnosed?

A person is diagnosed with Marfan syndrome based on clinical features such as aortic disease, dislocated lens, family history, and the presence of FBN1 mutations.

What treatments are available for Marfan syndrome?

While there is no cure for Marfan syndrome, treatments for clinical features include surgical repair of the aorta, removal and replacement of dislocated eye lenses, and the use of beta blockers and angiotensin receptor blockers like losartan to slow aortic dilation.

How does the inheritance pattern of Marfan syndrome work?

Marfan syndrome is an autosomal dominant disorder, meaning that a single mutated copy of the FBN1 gene is sufficient to cause the disease, even if there is a normal copy of the gene.