Marfan syndrome occurs in approximately 1 in every 5000 individuals. It is an autosomal dominant disorder therefore the majority of people with Marfan syndrome have a 50% chance of inheriting the defective gene from whichever parent who suffers from the disorder. Alternatively, in approximately 25-30% of those with Marfan syndrome the condition has developed due to a spontaneous mutation yielding the defective gene.
Marfan syndrome affects the body’s connective tissues – these are required for the body to maintain its structure and provide necessary structural support to other tissues and organs. Connective tissue is usually strong and resilient – it is made up of a number of proteins which include collagen, elastin and fibrillin.
In people with Marfan syndrome, a defect in the FBN1 gene located on chromosome 15 affects the production of the glycoprotein fibrillin (specifically fibrillin-1). Normally, molecules of fibrillin-1 bind together and form structures called microfibrils. The microfibrils are required to provide elasticity and support to connective tissues such as bones, tissues, muscles, and lenses of the eyes.
Microfibrils also store transforming growth factor beta (TGF-β), a protein which has a function in numerous cellular processes including the growth, differentiation and proliferation of cells. In this way, microfibrils are considered as the regulatory switch for TGF-β availability - TGF-β is inactivated when stored in microfibrils and is activated upon its release.
In Marfan syndrome, a defect in FBN1 results in irregularly-shaped microfibrils which cannot bind transforming growth factor beta (TGF- β). This results in an elevated level of tissue TGF- β and eventually problems in connective tissues throughout the body.
Connective tissue is widely distributed throughout the body as part of the bones, muscles, ligaments, blood vessels. Therefore it should be unsurprising that the symptoms are similarly dispersed. Fortunately, Marfan syndrome does not impact intelligence but it can affect the following areas and with variable degrees of severity:
Long bones are affected and grow longer than they should. People become tall with unusually long fingers, toes, arms and legs (arachnodactyly).
Lens dislocation (ectopia lentis) in one or both eyes occurs in more than 50% of those with the disorder. This happens because the connective tissue holding the lens in place becomes weak. As a result, the lens of the eye is held in an abnormal position so that the person is no longer looking through the center of the lens. Complications may occur i.e. retinal detachment, early onset cataracts or glaucoma, or extreme myopia (short-sightedness).
The most serious effects occur when the connective tissue in blood vessels become weakened and stretched. The aorta can become widened (aortic dilation) due to this which in turn increases the likelihood of tears (aortic dissection) and ruptures that allow leakage of blood into the atria of the heart.
Overly elastic valves may also result - in mitral valve prolapse, the valve between the left atrium and ventricle collapses backward and cannot close properly which can allow leakage of blood into the left atrium (regurgitation). The workload of the heart increases to prevent this backflow and can eventually lead to heart failure.
Decreased elasticity of the alveoli in the lungs could increase the likelihood of lung collapse should the alveoli become stretched.