Marfan syndrome

Marfan syndrome is a heritable disorder of connective tissue. It can affect the heart and blood vessels, eyes, and skeleton. In 1896 Dr. Antonine Jean Marfan, a French paediatrician, identified the disorder. Although Marfan syndrome was known since the end of the nineteenth century most of the details where discovered much later, between 1950 and 1990. In some of the following organ systems the Marfan syndrome may cause serious problems:

Heart and blood vessels

Enlargement and stretching of the aorta (“dilatation”) can cause a dissection or a rupture of the main blood vessel. This is a life threatening event and requires immediate surgery. A prolapse of the heart valves may also necessitate heart surgery.

Eyes

The main ophthalmologic symptoms are myopia, dislocated lenses and retinal detachment. These optical problems can be corrected by glasses, contact lenses or surgery.

Skeleton

Primary orthopaedic problems are curvature of the spine (scoliosis or kyphosis), inward or outward growth of the breastbone, long slender limbs, flat feet and claw or hammer toes. Surgery or a back brace are possibilities for treatment.

 

The severity of each symptom varies greatly among affected people and often gets more severe with age.

The Marfan syndrome is caused by mutations in the gene for fibrillin-1, known as FBN1. Such mutations generally are substitutions of individual nucleotides (“letters of the genetic code”) somewhere along the length of the gene, and usually affect critical amino acids (protein building blocks) of the protein fibrillin-1.

Fibrillin-1 has important functions in the organs affected by Marfan syndrome, and FBN1 mutations can lead with time to weakening of the fibrillin-1 rich tissues in these organs, which in turn leads to the manifestations of disease such as aortic dilatation. It is now possible to identify a FBN1 mutation in the great majority of patients with Marfan syndrome. It is not possible to repair the DNA mutation itself, and the treatment of Marfan syndrome concentrates on preventing the occurrence of the severe manifestations of disease. The most important aspect of treatment is the prevention of life threatening abnormalities of the aorta, involving medical treatment with beta blockers or losartan, regular monitoring, and if necessary, surgical replacement of the affected segment of the aorta.

(We thank PD Dr. P.N. Robinson for this comprehensive description.)

 

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