Primary trabeculodysgenesis in association with neonatal Marfan syndrome

We present the clinical and ophthalmological findings in two infants with neonatal Marfan syndrome (nMFS) and primary trabeculodysgenesis (PT). Fibrillin 1 (FBN1) mutations were confirmed in both cases. Numerous eye anomalies have been recognized in infants with nMFS, but PT has not been reported previously. Our report expands the phenotype of nMFS, and highlights the importance of early and careful ophthalmological assessment of these infants. (C) 2004 Wiley-Liss, Inc.

Histopathology and fibrillin-1 distribution in severe early onset Marfan syndrome

Marfan syndrome (MFS) is an autosomal dominant condition which may involve the cardiovascular, ocular, skeletal, and other systems. Mutations causing MFS are found in the FBN1 gene, encoding fibrillin-1, an extracellular matrix protein involved in microfibril formation. In the most severe cases, mutations are generally found in exons 24-32, and children with these mutations usually die in the first years of life, of cardiopulmonary failure. We present clinical, molecular and histopathological studies on a patient with severe early onset MFS. He has a mutation in exon 25 of FBN1, a G > A transition at nucleotide position 3131 that converts the codon TGC, coding for cysteine at position 1044, to TAC, coding for tyrosine (C1044Y). This has resulted in abnormalities of the extracellular matrix and a severe clinical phenotype, although he has survived to the age of 14 years. (c) 2005 Wiley-Liss, Inc.

Challenges in the diagnosis of Marfan syndrome

Marfan syndrome (MFS) is a multisystem disorder of connective tissue that is inherited in an autosomal dominant fashion, and results from mutations in the FBN1 gene on chromosome 15. Diagnosis is challenging as it requires definition of diverse clinical features and input from a variety of specialists. Genetic testing of FBN1 is time consuming, expensive and complex, and may not solve the diagnostic dilemma. Failure to make a diagnosis or making an inappropriate diagnosis of MFS has social, lifestyle and medical consequences for the individual as well as the family.

Overexpression of transforming growth factor-beta is associated with increased hyaluronan content and impairment of repair in Marfan syndrome aortic aneurysm

Background-Marfan syndrome (MFS), a condition caused by fibrillin-1 gene mutation is associated with aortic aneurysm that shows elastic lamellae disruption, accumulation of glycosaminoglycans, and vascular smooth muscle cell (VSMC) apoptosis with minimal inflammatory response. We examined aneurysm tissue and cultured cells for expression of transforming growth factor-beta1 to -beta3 (TGF beta 1 to 3), hyaluronan content, apoptosis, markers of cell migration, and infiltration of vascular progenitor cells (CD34). Methods and Results-MFS aortic aneurysm (6 males, 5 females; age 8 to 78 years) and normal aorta (5 males, 3 females; age 22 to 56 years) were used. Immunohistochemistry showed increased expression of TGF beta 1 to 3, hyaluronan, and CD34-positive microcapillaries in MFS aneurysm compared with control. There was increased expression of TGF beta 1 to 3 and hyaluronan in MFS cultured VSMCs, adventitial fibroblasts (AF), and skin fibroblasts (SF). Apoptosis was increased in MFS (VSMC: mean cell loss in MFS 29%, n of subjects = 5, versus control 8%, n = 3, P < 0.05; AF: 28%, n = 5 versus 7%, n = 5, P < 0.05; SF: 29%, n = 3 versus 4%, n = 3, not significant). In MFS, there was a 2-fold increase in adventitial microcapillaries containing CD34-positive cells compared with control tissue. Scratch wound assay showed absence of CD44, MT1-MMP, and beta-3 integrin at the leading edge of migration in MFS indicating altered directional migration. Western blot showed increased expression of TGF beta 1 to 3 in MFS but no change in expression of CD44, MT1-MMP, or beta-3 integrin compared with controls. Conclusions-There was overexpression of TGF-beta in MFS associated with altered hyaluronan synthesis, increased apoptosis, impaired progenitor cell recruitment, and abnormal directional migration. These factors limit tissue repair and are likely to contribute to aneurysm development.