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Exostoses, multiple, type I & II - Multiple exostoses type I (EXT1; MIM 133700) and type II (EXT2; MIM 133701) are autosomal dominant disorders characterized by multiple osteochondromas (MO). Osteochondromas are benign, cartilage-capped bone tumors.  Multiple osteochondromas arise from growth plates and are most numerous in the juxta-epiphyseal region of long tubular bones but also may occur from surfaces of flat bones, vertebrae and ribs.  Complications associated with osteochondromas include compression of nerves, tendons and blood vessels, short stature and deformities of bones leading to functional problems.  Considerable inter- and intrafamilial phenotypic variability is observed in MO.  Chondrosarcomas resulting in malignant transformation of osteochondromas occurs in about 1-5% of patients.  MO is caused by mutations in two genes, exostosin 1 (EXT1) and exostosin 2 (EXT2).  The products of these two genes are involved in the synthesis of heparin sulfate proteoglycans.  EXT1 and EXT2 are also considered to have tumor suppressor gene functions.  In general, a more severe phenotype has been associated with EXT1 mutations.

Deletion of the EXT1 and TRPS1 genes results in trichorhinophalangeal syndrome, type II (TRPS2; MIM 150230).  TRPS2 is also known as Langer-Giedion syndrome (LGS).  TRPS2 is a contiguous gene syndrome with the combined clinical features of trichorhinophalangeal syndrome, type I and multiple exostoses type I.