EXT1 EXT2

About EXT1 EXT2

EXT1 on chromosome 8q24.11 and EXT2 on chromosome 11p11.2 encode glycosyltransferases that work together in the Golgi apparatus to build heparan sulfate chains. Heparan sulfate proteoglycans are key components of the cell surface and extracellular matrix and act as co receptors that shape the distribution and signaling of hedgehog, FGF, WNT, and BMP proteins. Pathogenic variants in either gene cause hereditary multiple osteochondromas, also called hereditary multiple exostoses, an autosomal dominant disorder in which multiple benign cartilage capped bony growths, osteochondromas, develop near the growth plates of long bones during childhood and stop growing at skeletal maturity. EXT1 variants are more common and tend to cause more severe disease. Osteochondromas can cause skeletal deformities, short stature, limb length differences, restricted joint movement, and pain from pressure on nerves, tendons, or blood vessels. A small percentage of affected people develop a secondary chondrosarcoma arising in an osteochondroma, usually in adulthood. Surgery is used to remove symptomatic lesions and to correct deformities. The disorder illustrates the importance of morphogen gradients in skeletal development, since loss of heparan sulfate disrupts the signaling that coordinates growth plate cartilage.