Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EXOSTOSES, MULTIPLE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed2006

Correction and lengthening for deformities of the forearm in multiple cartilaginous exostoses.

BACKGROUND: Multiple cartilaginous exostoses cause various deformities of the epiphysis. In exostoses of the ulna, the ulna is shortened and the radius acquires varus deformity, which may lead to dislocation of the radial head. In this study, we present the results of exostoses resection, with correction and lengthening with external fixators for functional and cosmetic improvement, and prevention of radial head dislocation. METHODS: We retrospectively reviewed seven forearms of seven patients who had deformities of the forearm associated with multiple cartilaginous exostoses. One patient had dislocation of the radial head. Operative technique was excision of osteochondromas from the distal ulna, correction of the radius, and ulnar lengthening with external fixation up to 5 mm plus variance. We evaluated radiographs and the range of pronation and supination. Furthermore, we conducted a follow-up of ulnar length after the operation. RESULTS: Dislocation of the radial head of one patient was naturally reduced without any operative intervention. At the most recent follow-up, six of the seven patients showed full improvement in pronation-supination. Ulnar shortening recurred with skeletal growth of four skeletally immature patients; however, it did not recur in one skeletally mature patient. Overlength of 5 mm was negated by the recurrence of ulnar shortening about 1.5 years after the operation. CONCLUSIONS: We treated seven forearms of seven patients by excision of osteochondromas, correction of radii, and gradual lengthening of ulnas with external fixators. The results of the procedure were satisfactory, especially for function of the elbow and wrist. However, we must consider the possible recurrence of ulnar shortening within about 1.5 years during skeletal growth periods in immature patients.

Adolescent↗
PubMed2004

Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis).

Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature--bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in-frame G-to-C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted.

Base Sequence↗
PubMed2000

EXT 1 gene mutation induces chondrocyte cytoskeletal abnormalities and defective collagen expression in the exostoses.

Hereditary multiple exostoses (HME), an autosomal skeletal disorder characterized by cartilage-capped excrescences, has been ascribed to mutations in EXT 1 and EXT 2, two tumor suppressor-related genes encoding glycosyltransferases involved in the heparan sulfate proteoglycan (HSPG) biosynthesis. Taking advantage of the availability of three different exostoses from a patient with HME harboring a premature termination codon in the EXT 1 gene, morphological, immunologic, and biochemical analyses of the samples were carried out. The cartilaginous exostosis, when compared with control cartilage, exhibited alterations in the distribution and morphology of chondrocytes with abundant bundles of actin filaments indicative of cytoskeletal defects. Chondrocytes in the exostosis were surrounded by an extracellular matrix containing abnormally high amounts of collagen type X. The unexpected presence of collagen type I unevenly distributed in the cartilage matrix further suggested that some of the hypertrophic chondrocytes detected in the cartilaginous caps of the exostoses underwent accelerated differentiation. The two mineralized exostoses presented lamellar bone arrangement undergoing intense remodeling as evidenced by the presence of numerous reversal lines. The increased electrophoretic mobility of chondroitin sulfate and dermatan sulfate proteoglycans (PGs) extracted from the two bony exostoses was ascribed to an absence of the decorin core protein. Altogether, these data indicate that EXT mutations might induce a defective endochondral ossification process in exostoses by altering actin distribution and chondrocyte differentiation and by promoting primary calcification through decorin removal.

Adolescent↗
PubMed2005

Mice deficient in Ext2 lack heparan sulfate and develop exostoses.

Hereditary multiple exostoses (HME) is a genetically heterogeneous human disease characterized by the development of bony outgrowths near the ends of long bones. HME results from mutations in EXT1 and EXT2, genes that encode glycosyltransferases that synthesize heparan sulfate chains. To study the relationship of the disease to mutations in these genes, we generated Ext2-null mice by gene targeting. Homozygous mutant embryos developed normally until embryonic day 6.0, when they became growth arrested and failed to gastrulate, pointing to the early essential role for heparan sulfate in developing embryos. Heterozygotes had a normal lifespan and were fertile; however, analysis of their skeletons showed that about one-third of the animals formed one or more ectopic bone growths (exostoses). Significantly, all of the mice showed multiple abnormalities in cartilage differentiation, including disorganization of chondrocytes in long bones and premature hypertrophy in costochondral cartilage. These changes were not attributable to a defect in hedgehog signaling, suggesting that they arise from deficiencies in other heparan sulfate-dependent pathways. The finding that haploinsufficiency triggers abnormal cartilage differentiation gives insight into the complex molecular mechanisms underlying the development of exostoses.

Amino Acid Sequence↗