The Potential Role of the Elastic Fiber System in Adolescent Idiopathic Scoliosis.

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To assess its possible role in the etiology of adolescent idiopathic scoliosis, the elastic fiber system of the ligamentum flavum was examined in twenty-three patients who had scoliosis and in five age-matched individuals who did not. Elastic fibers are composed of two components: the amorphous core of elastin and microfibrils, of which fibrillin is the primary element. Fresh-frozen histological specimens of ligamentum flavum removed at the time of an operation were examined by Verhoeff staining for elastic fibers and by immunohistochemical staining with use of a monoclonal antibody to fibrillin. Additionally, cultures of fibroblast cells from the ligamentum flavum were used to study the biosynthesis and secretion of fibrillin and its incorporation into the extracellular matrix in vitro. The specimens from one patient did not provide sufficient material for the histological studies; however, fibroblasts were harvested from this specimen. In five (23 per cent) of the remaining twenty-two specimens from patients who had adolescent idiopathic scoliosis, Verhoeff staining of elastic fibers showed a marked decrease in fiber density (the number of fibers per unit area) and a non-uniform distribution of fibers throughout the ligament. Eighteen specimens (82 per cent) exhibited abnormalities on immunohistochemical staining, including a marked disarrangement of the fibers and a difference in the density of staining, when compared with the control specimens from individuals who did not have adolescent idiopathic scoliosis.Studies of the biosynthesis and secretion of fibrillin and its incorporation into the extracellular matrix in vitro demonstrated that fibroblasts from four (17 per cent) of the twenty-three specimens produced normal amounts of fibrillin and secreted it from the cell, but the fibrillin failed to bind to other macromolecules, to form a sedimentable complex, and to incorporate into the extracellular matrix. Collectively, the results suggest the potential role of the elastic fiber system as a component in the pathogenesis of adolescent idiopathic scoliosis in some individuals.CLINICAL RELEVANCEFibrillin, a large glycoprotein, is a component of the elastic fiber system. The current study shows that a small number of patients who have adolescent idiopathic scoliosis have a defect in the metabolism of fibrillin that precludes its incorporation into the sedimentable pericellular matrix.Mutations in the gene encoding for fibrillin cause the production of abnormal fibrillin that is not incorporated into the extracellular matrix.This lack of incorporation of fibrillin results in Marfan syndrome. Approximately 30 per cent of patients who have Marfan syndrome have defective incorporation of fibrillin in the pericellular matrix. Additionally, mutations in the fibrillin gene have been identified in a number of patients with Marfan syndrome who have scoliosis. These facts imply that patients who have adolescent idiopathic scoliosis and who demonstrate a defect in the incorporation of fibrillin into the intracellular matrix may have a mutation within the fibrillin gene. This mutation could result in scoliosis without the other phenotypic manifestations of Marfan syndrome. The possible relationship of the observed findings to a genetic basis will aid in the understanding of the causal association between genetic mutation and the clinical manifestations of disease. Knowledge of the etiological factors related to scoliotic deformities and spinal stability has direct bearing on the ability to modify current treatment modalities and to advise affected individuals.

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