Marfan syndrome: current perspectives

Abstract

Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor-1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity.

Pregnancy and Marfan syndrome

“…In the United States alone, estimated prevalence of MFS is 1 in 5,000, affecting both genders equally (2,5). Eighty percent of patients have some form of cardiovascular involvement, including aortic dilatation, aortic regurgitation and mitral and tricuspid valve prolapse with or without regurgitation (2,4,6).…”

“…Eighty percent of patients have some form of cardiovascular involvement, including aortic dilatation, aortic regurgitation and mitral and tricuspid valve prolapse with or without regurgitation (2,4,6). Although in the past life expectancy was reported to be greatly reduced, significantly better life expectancy due to improved medical and surgical treatment has been recently described (7).…”

“…MFS is caused by a mutation in the gene for MFS (FBN1) on chromosome 15q21, encoding the extracellular matrix protein fibrillin-1 (1,2). Recently, heterozygous mutations have also been identified in the gene encoding tissue growth factor-β receptor 2 (TGFBR2) on chromosome 3p24.…”

“…Marfan syndrome (MFS) is an autosomal dominant hereditary disorder of the connective tissue, in which involvement of the cardiovascular, skeletal, ocular and other systems may be present (1)(2)(3)(4). Pregnancy in MFS presents challenges to the clinician and the patient due to the increased incidence of maternal complications and involvement of the fetus, hence deserving special consideration.…”

Ocular Manifestations of Pediatric Systemic Disease

“…Marfan syndrome (MFS) is a genetic, systemic, connective tissue disorder from mutations in the FBN1 or fibrillin gene on chromosome 15 [22]. It primarily involves the skeletal, ocular, and cardiovascular systems.…”