Marfan syndrome

Marfan syndrome (MFS) is a genetic disorder of the connective tissue. The degree to which people are affected varies. People with Marfan tend to be tall and thin, with long arms, legs, fingers and toes. They also typically have flexible joints and scoliosis. The most serious complications involve the heart and aorta, with an increased risk of mitral valve prolapse and aortic aneurysm. Other commonly affected areas include the lungs, eyes, bones and the covering of the spinal cord. MFS is an autosomal dominant disorder. About 75% of the time, the condition is inherited from a parent, while 25% of the time it is a new mutation. It involves a mutation to the gene that makes fibrillin, which results in abnormal connective tissue. Diagnosis is often based on the Ghent criteria. There is no known cure for Marfan syndrome. Many people have a normal life expectancy with proper treatment. Management often includes the use of beta blockers such as propranolol or atenolol or, if that is not tolerated, calcium channel blockers or ACE inhibitors. Surgery may be required to repair the aorta or replace a heart valve. It is recommended that strenuous exercise be avoided. About 1 in 5,000 to 10,000 individuals have Marfan syndrome. It occurs equally in males and females. Rates are similar between races and in different regions of the world. It is named after Antoine Marfan, a French pediatrician who first described the condition in 1896. More than 30 different signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect the skeletal, cardiovascular, and ocular systems, but all fibrous connective tissue throughout the body can be affected. Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above-average height, and some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes. Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal lateral curvature of the spine (scoliosis), thoracic lordosis, abnormal indentation (pectus excavatum) or protrusion (pectus carinatum) of the sternum, abnormal joint flexibility, a high-arched palate with crowded teeth and an overbite, flat feet, hammer toes, stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones, and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets. In Marfan syndrome, the health of the eye can be affected in many ways, but the principal change is partial lens dislocation, where the lens is shifted out of its normal position. This occurs because of weakness in the ciliary zonules, the connective tissue strands which suspend the lens within the eye. The mutations responsible for Marfan syndrome weaken the zonules and cause them to stretch. The inferior zonules are most frequently stretched resulting in the lens shifting upwards and outwards, but it can shift in other directions as well. Nearsightedness and blurred vision are common, but farsightedness can also result particularly if the lens is highly subluxated. Subluxation (partial dislocation) of the lens can be detected clinically in 80% of people with Marfan syndrome by the use of a slit-lamp biomicroscope. If the lens subluxation is subtle, then imaging with high-resolution ultrasound biomicroscopy might be used. Other signs and symptoms affecting the eye include increased length along an axis of the globe, myopia, corneal flatness, strabismus, exotropia, and esotropia.