Disease relevance of Exostoses

• Multiple osteochondromatosis or hereditary multiple exostoses (EXT) is an autosomal dominant inherited disorder characterized by the presence of multiple benign cartilage-capped exostoses [1].
• Sutural exostoses, rib hyperostoses, craniosynostosis, mental retardation with focal fat deposition: Proteus syndrome [2]?
• Two adult patients with multiple hereditary exostoses, a skeletal disorder with recognized malignant potential, each demonstrated increased 99mTc diphosphonate uptake in an exostosis in which renewed growth had begun [3].
• beta-Aminopropionitrile (BAPN) administered to rats has caused exostosis formation at sites of muscle attachment and also caused delay in the healing of soft tissue wounds and of bone fractures [4].
• Technetium-99m diphosphonate scintigraphy of 11 benign exostoses and nine exostotic chondrosarcomas was correlated with pathologic macrosections of the resected tumors [5].

High impact information on Exostoses

• Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors (exostoses) [6].
• Mice deficient in Ext2 lack heparan sulfate and develop exostoses [7].
• A mutation in tout-velu, a gene related to the vertebrate Exostoses 1 heparan sulfate co-polymerase, likewise does not affect chondroitin sulfate synthesis but reduces all forms of heparan sulfate to below the limit of detection [8].
• Two genes, EXT1 and EXT2, and at least one other unidentified gene, are known to be involved in the formation of exostoses [9].
• Western blot analysis shows that exostosis chondrocytes from two out of three patients aberrantly produce high levels of muscle-specific alpha-actin, whereas beta-actin levels are similar to normal chondrocytes [10].

Chemical compound and disease context of Exostoses

• The neurologic complication was caused by an exostosis, arising from the C2 right hemilamina, compressing the spinal cord [11].
• Rats that were given both BAPN and phenytoin produced similar exostoses as rats that were given BAPN alone [4].
• Two measures of heavy occlusal function--periodontal ligament (PDL) width and occlusal attrition--were analyzed for their relationship to three parameters of buccal alveolar bone (exostoses, lipping, and overall thickness) [12].
• The exostosis was excised 10 weeks after initial presentation, with warfarin being continued for four weeks postoperatively [13].
• Skeletal fluorosis (mottled teeth in pups, bony exostoses in adults) followed use of a commercial dog food later found to contain 460 ppm fluoride (F) from rock phosphate added as a mineral source [14].

Biological context of Exostoses

• We and others have previously suggested that a two-hit mutational model applies to the development of an exostosis where a germline mutation coupled with a somatic mutation results in the loss of EXT1 or EXT2 function and subsequent tumor formation [15].
• Multiple osteochondromas (hereditary multiple exostoses, diaphyseal aclasis, cartilagenous exostoses) are anomalies of bone development in which multiple cartilagenous exostoses grow out from the cortical surface, mainly involving ends of the long bones [16].

Anatomical context of Exostoses

• Heparan sulfate abnormalities in exostosis growth plates [17].
• Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterized by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses [18].
• A male surfer who has surfed regularly for 20 years or more has a one in two chance of developing significant obstruction of the external ear canal resulting from exostoses and this is a three in seven chance for females [19].
• The presence of unilateral external auditory canal exostoses in a patient who is not a swimmer or surfer is suggestive of PS [20].
• Alveolar ridge exostoses formation as a response to habitual occlusal stress: a case report [21].

Gene context of Exostoses

• Two homologous genes, EXT1 and EXT2, responsible for the development of benign multiple cartilagenous bone tumors (exostoses) on the long bones, have been identified in the past 2 years [22].
• Because collagen molecules are important for tissue remodeling during physiologic growth and differentiation, both COL12A1 and COL4A5 constitute good candidate target genes in the pathogenesis of subungual exostosis [23].
• The donor patients' ages ranged from 1 to 90 years and their disease states included congenital limb anomalies, exostosis, and osteo- and rheumatoid arthritis [24].
• Finally, we propose that the development of exostoses in the human Hereditary Multiple Exostoses syndrome can be attributed to activation of Ihh signaling [25].
• The content of urokinase-type plasminogen activator increased, while the concentration of tissue-type plasminogen activator decreased in bone tumors of various histological compositions compared to osteochondral exostoses [26].

Analytical, diagnostic and therapeutic context of Exostoses

• On the other hand, exostoses in patients with multiple exostoses (osteochondromas) showed varying appearances in roentgenography and had cartilage caps on their surfaces [27].
• A patient with hereditary multiple exostoses and myelopathy caused by an exostosis originating from the posterior aspect of the T5 vertebral body was treated with a staged anterior decompression/corpectomy and posterior spinal fusion [28].

References