Hereditary multiple exostoses

Hereditary multiple exostoses (HME) is a rare medical condition in which multiple bony spurs or lumps (also known as exostoses, or osteochondromas) develop on the bones of a child. HME is synonymous with Multiple hereditary exostoses and Multiple osteochondromatosis, which is the preferred term used by the World Health Organization.

Pathophysiology
HME is estimated to occur in 1 in 50,000 people. It is characterized by the growth of cartilage-capped benign bone tumours around areas of active bone growth, particularly the metaphysis of the long bones. HME can lead to the shortening and bowing of bones, as such affected individuals often have a short stature. Depending on their location the exostoses can cause the following problems: pain or numbness from nerve compression, vascular compromise, inequality of limb length, irritation of tendon and muscle, as well as a limited range of motion at the joints upon which they encroach. Generally, when a person with HME reaches maturity, and their bones stop growing, the exostoses also stop growing. A person with HME is also more likely to develop a rare form of bone cancer called chondrosarcoma as an adult.

Treatment
HME begins to manifest itself in childhood and currently has no cure. Surgery, physical therapy and pain management are currently the only options available to HME patients, but success varies from patient to patient and many struggle with pain, fatigue and mobility problems throughout their lives. It is not uncommon for HME patients to undergo numerous surgical procedures throughout their lives to remove painful or deforming exostoses, correct limb length discrepancies or improve range of motion.

Genetics
HME is an autosomal dominant hereditary disorder. This means that a patient with HME has a 50% chance of transmitting this disorder to his or her children. Most individuals with HME have a parent who also has the condition, however, approximately 10% -20% of individuals with HME have the condition as a result of a spontaneous mutation and are thus the first person in their family to be affected.

HME has thus far been linked with mutations in three genes. which maps to chromosome 8q24.1, which maps to 11p13 , and  which maps to the short arm of Chromosome 19 (though its exact location has yet to be precisely determined). Mutations in these genes typically lead to the synthesis of a truncated EXT protein which does not function normally. It is known that EXT proteins are important enzymes in the synthesis of heparan sulfate, however the exact mechanism by which altered synthesis of heparan sulfate could lead to the abnormal bone growth associated with HME is unclear. It is thought that normal chondrocyte proliferation and differentiation may be affected, leading to abnormal bone growth.

For individuals with HME who are considering starting a family, preimplantation genetic testing and prenatal diagnosis are available to determine if their unborn child has inherited the disease. HME has a 96% penetrance, which means that if the disease is indeed transmitted to a child, he/she will have a 96% of actually manifesting the disease, and 4% chance of having the disease but never manifesting it.