Marfan Syndrome (Síndrome de Marfan)

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1 Felipe Antônio Dal'Agnol 
MARFAN SYNDROME 
Marfan syndrome is a genetic disorder that results in defective connective tissue, 
which can affect a person's skeleton, heart, blood, vessels, eyes, and lungs. 
Normally, the interstitial space of various body tissues is full of microfibrils - which are 
strong ropelike structures that provide tissue integrity and form connective tissue. The 
main component of microfibrils is a glycoprotein called fibrillin. In some structures 
microfibrils form a scaffold for additional proteins like elastin. 
Elastin fibers are highly cross-linked, and that gives them a rubber-band-like quality, 
which allows tissues to stretch and then spring back to their original shape. Tissues 
that have elastin fibers are tissues like the arteries, skin, and lungs, and tissues that 
have microfibrils but no overlying layer of elastin are like tendons and the ciliary 
zonules that hold the eye lens in place (these tissues are less stretchable, but still have 
considerable tensile strength). 
In addition to being part of microfibrils, fibrillin also regulates tissue growth: fibrillin 
sequesters or removes transforming growth factor beta, or TGF-β, which stimulates 
tissue growth, so fibrillin therefore lowers how much TGF-β is available to stimulate 
growth. 
Marfan syndrome is caused by mutations in a gene called FBN1, or fibrillin 1, on 
chromosome 15. It's autosomal dominant, which means that even if there's a normal 
copy of the gene, a single mutated copy of the gene (heterozygous mutations) is 
sufficient to cause the disease. The FBN1 gene encodes Fibrillin-1 protein, one of three 
fibrillin subtypes. 
In Marfan syndrome, fibrillin-1 is either dysfunctional or less abundant. As a result, 
there are fewer functioning microfibrils in the extracellular matrix, and that means 
there's less tissue integrity and elasticity. 
Additionally, TGF-β doesn't get effectively sequestered, so TGF-β signaling is excessive 
in these tissues - meaning more growth. 
The most obvious physical features of Marfan syndrome involve the skeleton: the long 
bones grow excessively, so individuals are tall with long arms and legs - this is called a 
Marfanoid body habitus. They have long, thin fingers and toes too, called 
arachnodactyly. Finally, overgrowth of ribs can cause pectus excavatum or pectus 
carinatum. Other bone and joint features include scoliosis where the spine has a 
sideways curve, an inability to extend the elbows all the way to 180 degrees, flexible 
joint, a downward slant to the eyes, and a narrow palate that crowds the teeth. 
In the skin, Marfan syndrome can cause stretch marks, and in the lung it can cause 
bullae to form (large spaces that replace the normal architecture of the lungs and can 
 
2 Felipe Antônio Dal'Agnol 
cause a pneumothorax to form. In the eyes, Marfan syndrome is a risk factor for retinal 
detachment and a dislocation of the lens, which is usually in an upward direction. 
The most serious features of Marfan syndrome are cardiovascular. 
 The aorta dilates over time, which is a risk for aortic valve insufficiency, where 
blood leaks back into the left ventricle during diastole. 
 The aorta also undergoes cystic medial necrosis, which is where there is 
degeneration of the tunica media, which is the central portion of the aortic 
wall. 
 Both dilation and cystic medial necrosis weaken the aorta, making it susceptible 
to aneurysm, dissection, and rupture. All of these complications can be fatal. 
 Finally, Marfan syndrome is a risk factor for mitral valve prolapse, where the 
mitral valve pouches into the left atrium during systole. 
The features of Marfan syndrome, though, might not be present for everyone with 
Marfan syndrome, and any given feature can be more or less severe. Also, Marfan 
syndrome isn't usually noticeable at birth, so the symptoms show up over time as the 
child grows. Occasionally, features are present at birth, called early-onset or neonatal 
Marfan syndrome. 
Diagnosis 
A person is diagnosed with Marfan syndrome if they have clinical features of Marfan 
syndrome like aortic disease, a dislocated lens, family history, and FBN1 mutations. 
Treatment 
Although there is no cure for Marfan syndrome but there are treatments for some of 
the clinical features. For example: 
 If an eye lens dislocates, it can be remove and replace by an artificial lens. 
 If the aorta gets too wide, it can be repaired surgically so it doesn't dissect or 
rupture. Beta blockers have been shown to slow aortic dilation, and the 
angiotensin receptor blocker losartan, which decreases TGF-β signaling, can 
slow dilation even more when given in conjunction with the beta blocker.