fibrin and Marfan-Syndrome

Marfan syndrome is an autosomal dominant disorder, characterized by tall stature, long arms and legs, ectopia lentis, and aortic aneurysms and dissections. Recent research has revealed that these phenotypes are caused by mutations in fibrillin-1, the major structural component of elastic microfibrils, and the continuing dysregulation of transforming growth factor beta (TGFbeta) signaling is principally considered to be contributing to the pathophysiological background of the disease. Blockade of TGFbeta signaling by angiotensin II receptor antagonism is a novel promising therapeutic option, and thus such large clinical randomized controlled trials are underway. Here, we review the past development, current status and future perspectives in the research field for Marfan syndrome.

Topics: Fibrin; Humans; Marfan Syndrome; TGF-beta Superfamily Proteins

The mechanisms implicated in the clinical manifestations of zonular diseases, especially ectopia lentis, are reviewed.. The molecular mechanisms involve fibrillin in a large spectrum of heritable diseases characterized by zonular stretching. The usual complications are refractive errors, especially myopia, glaucoma (either primary open angle, secondary angle closure and pupil block by anterior displacement of the lens) and retinal detachment.. The genetics and molecular understanding provide information for genetic counseling. Treatment of myopia and glaucoma depend on the underlying mechanism, and lens surgery techniques are continuously improved.

Topics: Ectopia Lentis; Fibrin; Glaucoma; Humans; Marfan Syndrome; Refraction, Ocular; Refractive Errors

Loeys-Dietz syndrome (LDS) is a connective tissue disease caused by mutations in the genes encoding the transforming growth factor-beta receptor (TGFBR). LDS is associated with aneurysms or dissections of the aorta similar to Marfan syndrome (MFS) as well as arterial tortuosity and aneurysms in the peripheral arteries. The purpose of this study was to evaluate the arterial diseases of LDS to differentiate it from MFS.. A total of 10 LDS patients with an identified mutation in TGFBR (6 male, 4 female; mean age 36.3 years) and 20 MFS patients with an identified mutation in fibrilin-1 who were age- and sex-matched to the LDS subjects (12 male, 8 female; mean age 37.1 years) were reviewed. The prevalence of vertebral arterial tortuosity (VAT) and peripheral aneurysm (PAN) was studied using computed tomography angiography.. In all, 9 of the 10 LDS patients had VAT, and five PANs were observed in 3 patients. In contrast, 8 (40%) of the MFS patients had VAT, and 1 patient had a PAN. LDS had a higher prevalence of VAT (P = 0.017) by Fisher's exact test.. The VAT was highly prevalent among LDS patients. Thus, the presence of VAT has the potential to differentiate LDS from MFS.

Topics: Adult; Aneurysm; Chi-Square Distribution; Female; Fibrin; Humans; Loeys-Dietz Syndrome; Male; Marfan Syndrome; Middle Aged; Radiographic Image Interpretation, Computer-Assisted; Receptors, Transforming Growth Factor beta; Tomography, X-Ray Computed; Vertebral Artery

The large glycoprotein fibrillin is a structural component of elastin-containing microfibrils found in many tissues. The Marfan syndrome has been linked to the fibrillin gene on chromosome 15, but congenital contractural arachnodactyly, which shares some of the physical features of the syndrome, has been linked to the fibrillin gene on chromosome 5.. Using specific markers for the fibrillin genes, we performed genetic linkage analysis in 28 families with the Marfan syndrome and 8 families with four phenotypically related disorders--congenital contractural arachnodactyly (3 families), ectopia lentis (2), mitral-valve prolapse syndrome (2), and annuloaortic ectasia (1).. Genetic linkage was established between the Marfan syndrome and only the fibrillin gene on chromosome 15, with a maximum lod score of 25.6 (odds for linkage, 10(25.6):1). Ectopia lentis was also linked to the fibrillin gene on chromosome 15, whereas congenital contractural arachnodactyly was linked to the fibrillin gene on chromosome 5. There was no linkage of mitral-valve prolapse to the fibrillin gene on chromosome 5; studies of chromosome 15 were not informative. Annuloaortic ectasia was not linked to either fibrillin gene.. The Marfan syndrome appears to be caused by mutations in a single fibrillin gene on chromosome 15. Diagnosis of the Marfan syndrome by genetic linkage and analysis is now feasible in many families.

Topics: Base Sequence; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 5; Ectopia Lentis; Female; Fibrin; Genetic Linkage; Humans; Lod Score; Male; Marfan Syndrome; Mitral Valve Prolapse; Molecular Sequence Data; Phenotype