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Marfan syndrome (MFS) is an autosomal dominant genetic disease, with an estimated frequency of 5/10,000 and a neomutation rate of 20% of reported cases (ie, 20% of the affected patients have no parents affected). It affects both males and females equally worldwide and carries an increased risk of aortic dilatation, dissection and rupture, which are responsible for the increased mortality. The syndrome also affects the mitral valve and possibly the myocardium, 1 eyes (sometimes leading to blindness), skeleton, skin and integuments, lungs and neurological system. These features appear and develop with age as they are usually the consequence of altered resistance of the tissues. The definition of the syndrome has evolved throughout the 20th century, illustrating the difficulty in diagnosis. MFS is usually related to mutations in the fibrillin 1 (FBN1 ) gene, encoding fibrillin 1, a major adhesive protein of the extracellular matrix, homopolymerised and organised as microfibrils. Great progress has been made in patient care, which has led to improved survival: it is generally recognised that 30 years of life has been gained during the last 30 years. 2 Recent progress in understanding pathophysiology has led to great expectations for further improvement in the near future.
The evolution of MFS through the years
Professor A. Marfan was a French paediatrician of the late 19th century who described the princeps case of a 5-year-old girl (named Gabrielle) who had a specific skeletal phenotype associating 'dolichostenomelia' and 'arachnodactyly'. She died at the age of 12 from tuberculosis. After this initial description, further aspects of the syndrome were recognised, notably ocular involvement and cardiac features with aortic enlargement and rupture. It is not obvious that the princeps case had this risk, that is, that Gabrielle had an aortic risk; however, since then, the terminology of MFS has remained associated with the aortic risk, while the skeletal features associated with little aortic risk have been recognised as congenital contractural arachnodactyly, or Beals syndrome, which is now known to be related to mutations in the FBN2 gene encoding fibrillin 2.
Successive expert meetings have been held, which, over time, defined more and more precisely what should be coined 'Marfan syndrome' in the present day. 3-5 Molecular genetics (ie, mutation of the FBN1 gene) has been repeatedly...