MARFAN-SYNDROME - CURRENT MEDICAL AND GENETIC KNOWLEDGE - HOW TO TREAT AND WHEN

Marfan syndrome (MFS), first described 100 years ago, remains a clinic al diagnosis. Two out of 3 major systems (ocular, cardiac, skeletal) m ust be classically affected, to avoid overdiagnosis. Diagnosis may be confirmed by linkage to the dominantly inherited gene MFS-1 on 15q21, or by discovering the family mutation. Either technique may be used fo r prenatal diagnosis. Modern medical and surgical management is prolon ging life, by on average, 13 years, with postoperative 20 year surviva l rate 65%. Beta-blocker therapy slows aortic root dilatation, and ele ctive surgery is offered at ascending aorta diameter greater than or e qual to 5 cm. Known associations with early death include new mutation , family history of dissection < 5 cm, male sex, and emergency surgery where the death rate is 5 times higher than in elective surgery. Preg nancy bears a 1% risk of fatal complication, and this risk rises with increasing aortic root diameter. Caesarean section at 38 weeks gestati on should be offered if aortic root diameter is greater than 4.5 cm. G ene mapping reveals almost every mutation to be unique, interfering wi th multimerization of fibrillin monomers, or interactions with other c onnective tissue elements. Neonatal MFS is caused by mutations in exon s 24-32, in calcium-binding EGF-like sequences. Mutations affecting cy steines or aminoacids critical for calcium binding in other EGF-like d omains, or deletions of complete EGF-like domains, generally lead to c lassical MFS phenotypes, as do mutations in TGF receptor-like domains. Heterogeneity has been reported with a second locus (MFS-2) on chromo some 3 in one French pedigree.