Marfan Syndrome, A Review

Abstract

Marfan syndrome is named after the French pediatrician Antoine Bernard-Jean Marfan who described in 1896 a girl with arachnodactyly and long limbs1. The patient also had congenital contractures of the elbows and would not fulfill the current criteria for Marfan syndrome. She probably was suffering from a condition that we now call contractural arachnodactyly, caused by mutations in the FBN2 gene.The clinical features of Marfan syndrome affect many systems of the body. The most obvious are the skeletal features, long limbs, tall stature, long thin fingers (arachnodactyly or spider fingers). The skeletal features can be scored objectively as: arm span more than 1.05 x body length; wrist sign (thumb and index finger can encircle the wrist of the other hand with at least one digit overlap) and thumb sign (when making a fist around the thumb, one digit of the thumb sticks out). The main neurological symptom is dural ectasias. The most severe symptoms are cardiovascular: mitralis valve prolapse, aortic dilatation and thoracic aortic aneurysms and dissections, which may lead to sudden death5. However, I noticed in discussions with patients that they often consider the ocular symptoms, severe myopia and lens luxation, the worst for themselves, because the latter may lead to blindness.

Growth of the aortic root in children and young adults with Marfan syndrome

“…9 To correct for height and weight differences, Z-scores were calculated by using the normogram published by Pettersen et al 10 Pathogenic FBN1 variants were classified according to the European Molecular Genetics Quality Network (EMQN) guidelines and as described in the recent publication by GP, coauthor of this article. 11 Patients with MFS were stratified into two groups based on the effect of the FBN1 mutation on the production of the FBN1 protein: (1) haploinsufficient (HI) FBN1 mutation carriers, in which the production of normally functioning FBN1 protein is decreased, and (2) dominant negative (DN) FBN1 mutation carriers, in which a mutant FBN1 protein interferes with the normally functioning FBN1 protein. 12 13 FBN1 mutations were classified as HI and DN according to the criteria described by Franken et al 14 In addition, FBN1 variants with a DN effect were further classified by their effect on the cysteine content in the FBN1 protein, since recent work has suggested an important phenotype correlation.…”