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 rope-like structures that provide tissue integrity and form connective tissue.

Each microfibril is made of cellulose as well as glycoproteins including the protein 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 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 – in other words a heterozygous mutation – 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 less abundant or it is dysfunctional. As a result, there are fewer functioning microfibrils in the extracellular matrix, and that means there’s less tissue integrity and elasticity.

Connective tissue is found throughout the body, so this can affect nearly every body system.

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, a reference to the long legs of spiders.

Finally, overgrowth of ribs can cause pectus excavatum, where the chest sinks in, or pectus carinatum, where the chest points out.

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 joints, 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 lungs it can cause bullae to form. These are large spaces that replace the normal architecture of the lungs and can 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.