Written by Susan   
Dec 19, 2013 at 09:02 AM

What is MHE?

Multiple Hereditary Exostoses (“MHE”) is a genetic bone disorder in which benign cartilage-capped tumors (exostoses or osteochondromas) grow from the growth plates of long bones or from the surface of flat bones throughout the body.   These exostoses can cause numerous problems, including: compression of peripheral nerves or blood vessels; irritation of tendons and muscles resulting in pain and loss of motion; skeletal deformity; short stature; limb length discrepancy; chronic pain and fatigue; mobility issues; early onset arthritis; and an increased risk of developing chondro- sarcoma. MHE patients have a 50% chance of passing this disorder on to their children.

It is not uncommon for MHE patients to undergo numerous surgical procedures throughout their lives to remove painful or deforming exostoses, or to correct limb length discrepancies or improve range of motion.  Surgery, physical therapy and pain management are currently the only options available to MHE patients, but their success varies from patient to patient and many struggle with pain, fatigue and mobility problems throughout their lives.

The MHE Coalition provides support and information to families living with this rare bone disorder. Support includes development and distribution of information about this condition to patients, families and health care providers; telephone and email support to patients and their families; assistance in finding qualified doctors and surgeons; publication of a newsletter focusing on research and clinical issues and areas of concern to our membership; and an informative web site which provides information for patients, researchers and physicians. Our Internet Resource Library contains the largest collection of MHE-related links.

We  co-authored with members of our Medical Advisory Board and various specialists who graciously shared their time and expertise with our organization, a book entitled “The ABC’s of MHE."  This book serves as a guide for patients and physicians alike and is available in print and on our web site.  One of our goals is to educate the medical community as well as the MHE community on the day-to day realities of life with this disorder, and to provide a standard of care and better understanding of treatment options.

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:[1]

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[2] 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.[2] Problems may be had in later life and these could include weak bones and nerve damage.[3][4][5] The reported rate of transformation ranges from as low as 0.57%[6] to as high as 8.3% of people with HME.[7]


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.

  • EXT1 which maps to chromosome 8q24.1[8]
  • EXT3 which maps to the short arm of Chromosome 19 (though its exact location has yet to be precisely determined)[10]

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.[11][12] 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.[13]

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 affected gene is indeed transmitted to a child, the child will have a 96% of actually manifesting the disease, and 4% chance of having the disease but never manifesting it. It should be noted that the 96% penetrance figure comes from one study.[14] Other studies have observed both incomplete and variable penetrance but without calculating the % penetrance, e.g.[15] In both the aforementioned studies the symptomless individuals carrying the faulty gene were predominantly female, leading to speculation that incomplete penetrance is more likely to be exhibited in females. Indeed, other work has shown that boys/men tend to have worse disease than females, as well as that the number of exostoses in affected members of the same family can vary greatly.[16] It is also possible for females to be severely affected.

Symptoms are more likely to be severe if the mutation is on the ext1 gene rather than ext2 or ext3; ext1 is also the most commonly affected gene in patients of this disorder.[16]

Clinical features

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.


Diagnosis is mostly clinical and radiological. Technetium skeletal scintigrams are occasionally used to determine number of exostoses.[17]


Surgical excision is performed when exostoses lead to growth disturbances or lead to disability. Knee osteotomies are associated with high incidence of peroneal nerve paralysis.[1]

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.[4][18]


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Last Updated ( Jun 21, 2014 at 03:12 AM )


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