Hereditary multiple exostoses
|Hereditary multiple exostoses|
|Classification and external resources|
Photograph of the legs of a 26-year-old male showing multiple lumps leading to deformity.
Hereditary multiple exostoses (HME or MHE), also known as Diaphyseal aclasis, 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.
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. Typically five or six exostoses are found in upper and lower limbs.Most common locations are:
HME can lead to the shortening and bowing of bones; 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, Madelung's deformity as well as a limited range of motion at the joints upon which they encroach. A person with HME has an increased risk of developing a rare form of bone cancer called chondrosarcoma as an adult. Problems may be had in later life and these could include weak bones and nerve damage.  The reported rate of transformation ranges from as low as 0.57% to as high as 8.3% of people with HME.
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.
- EXT3 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 that 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.Since the HME genes are involved in the synthesis of a glycan (heparan sulfate), HME may be considered a congenital disorder of glycosylation according to the new CDG nomenclature suggested in 2009.
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.
HME can cause pain to people of all ages. To children, this can be especially painful. During exercise, it can cause a significant amount of pain. Exostoses may be visible to naked eye from outside. Multiple deformities, as mentioned above, can be present.
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. Usually the treatment can be problematic. The osteochondromas can return in the same places and may be more painful.
Possible Connection to Autism
Some parents of children with MHE have observed autism-like social problems in their children. To explore those observations more deeply, a 2012 study by the Sanford-Burnham Medical Research Institute used a mouse model of MHE to observe cognitive function. The findings indicated that the mutant mice endorsed three autistic characteristics: social impairment, language deficits, and repetitive behavior.
One of the study's authors, Yu Yamaguchi, M.D., Ph.D., expressed his appreciation for parents' involvement in the study. “I can’t emphasize enough how much it helped that the parents of kids with MHE got involved and supported this research," he said. "As parents, they noticed their kids had social problems that gave them challenges at school. School officials and other people didn’t take these observations seriously – they usually just waved off the problems, assuming that the kids’ bone deformities just make them shy. This latest research doesn’t solve any bone issues for MHE patients, but it does help support what the parents always knew – these children need special care.”
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- Hereditary Multiple Exostoses (MHE) Research Foundation's Website
- Medcyclopaedia - Hereditary Multiple Exostises
- GeneReviews: Hereditary Multiple Exostoses
- Information about Multiple Hereditary Exostoses (MHE)
- Hereditary Multiple Exostoses Support Group
- Images of Multiple Hereditary Exostoses (MHE) from Medical Image Database - MedPix