Summary
Marfan syndrome (MFS) is an autosomal dominant disease with an estimated prevalence of 1/5,000 individuals. Diagnostic criteria for MFS were established in Berlin in 1986. All systems susceptible of being involved were collected, and then the major clinical signs and other minor manifestations according to the type of involvement were defined, with the presence of a certain number of clinical signs in a system establishing whether or not the individual is affected with MFS. With time, weaknesses in the Berlin criteria became evident, accentuated in particular by the development of molecular biology tests, and led de Paepe et al (1996) to revise them. At present, both sets of criteria can be used; their discriminating abilities are being evaluated. The clinical signs in MFS are mainly musculoskeletal (dolichostenomelia, arachnodactyly, joint hypermobility, spinal involvement, acetabulum protrusion, thoracic skeletal involvement), ocular (dislocated lens, axial myopia) and cardiac; this latter conditions the prognosis as a function of the severity of mitral and aortic valve anomalies. Patients with MFS should be followed by clinicians belonging to different specialties but working together within the framework of multidisciplinary consultations (cardiology, genetics, ophthalmology, pediatrics, rheumatology). Cardiovascular therapies can be proposed. MFS is a fibrillinopathy resulting from defective fibrillin-1 synthesis. The gene coding for this protein (FBN1) has been partially cloned and was localized to chromosome 15q21 in humans. At present, more than 400 mutations of the FBN1 gene have been described. A second gene implicated in MFS (called MFS2) was localized to the short arm of chromosome 3 at 3p25. This gene and the protein that it encodes are still unknown. It is currently estimated that alterations of this gene could explain 8 to 15% of the MFS cases. MASS syndrome is a heritable disorder of connective tissue characterized by involvement of the Mitral valve, Aorta, Skeleton, and Skin. The MASS syndrome is also due to a mutation in FBN1, the fibrillin 1 gene (i.e the same gene as is mutated in Marfan syndrome).* Author: Prof J-M LeParc (February 2005)*.
