The Lubkin Fund for MHE Research
About MHE

Genetics

Multiple Hereditary Exostosis (MHE) is an autosomal dominant bone disorder. This means that there is a 50% chance of passing on this disorder when one parent carries the gene.  MHE is a rare disease that occurs in 1 in every 50,000 children. While approximately 80% of all sufferers have one parent who is affected, there is an approximately 20% chance of inheriting the gene spontaneously.

MHE is characterized by the growth of numerous cartilage-capped bony tumors that develop next to the growth plates of all the long bones as well as arising from the flat bones like the scapula, ribs and pelvis. The growth of these exostosis continue until puberty ends. Approximately 2-4% of those afflicted  will have an exostosis that will suffer from malignant transformation and turn into chondrosarcoma or osteosarcoma during adulthood.

Two genes have been identified as causing MHE, Exostosin-1(EXT1) and Exostosin-2 (EXT2).  EXT1 was first identified as a gene involved in the development of MHE in 1995. EXT2 was later identified in 1996. EXT1 and EXT2 act as tumor suppressor genes.  It is believed that 50% of MHE patients have the EXT1 gene and 30% have the EXT2 gene. There are many patients whose genotype has not been identified. EXT1 and EXT2 are tumor suppressor genes and when mutated allow tumors or exostosis to arise from the long and flat bones.

Although two genes, EXT1 and EXT2 have been identified, the science is not mature enough to provide a cure for those affected, treat the symptoms or provide gene therapy to end the generational mutations.


Manifestations

 In addition to the development of the bony tumors, MHE patients frequently suffer from progressive skeletal deformities including limb length inequality, bowing of the limbs, and angular deformities of the joints.  Pain occurs from soft tissue trauma, including bursa formations, as well as from ligament tears, and nerve or vascular deviations, impingements, entrapment or injury. Both neurologic and vascular problems can occur as a result of these complications. Some patients suffer with peripheral neuropathy and peroneal nerve palsy.

Removal of the exostosis or tumor is the only method available to deal with the pain and complications that occur. Some tumors are so interconnected with the surrounding structure, including nerves, arteries and ligaments, that complete removal of the cartilage cap is impossible.  When part of the cartilage cap is left, exostosis will often regrow. In addition, the surgeries have many possible side effects, including nerve damage and wound healing complications. Current research indicates that there is a correlation between MHE and wound healing/scarring problems.

There are several surgical options to deal with the skeletal deformities. They include stapling of the growth plate in a growing child to try to correct the angular deformity. This procedure is intended to be reversed and must be timed properly and with precision so as not to shut down the growth plate permanently.  In an osteotomy, the surgeon cuts the bone and realigns it. Hardware is required to hold the bones in place while they heal. Lastly, External Fixators  are used by surgeons to correct either the angular deformity or the limb length inequality. The fixator is surgically implanted and held in place by a set of pins.  The fixator can be programmed to distract and lengthen the bone, and to correct the angle of growth.  All of these procedures have significant risks and pain associated with them.

It is important to remember that surgical intervention is not always possible or successful.

Sample X-Rays



Above is an example of an exostosis growing in between the bones of the ankle. The bone is both remodelling the tibia and causing joint deformity.


This is the same ankle post surgery. An osteotomy and bone graft were performed to correct the bone remodelling and the ankle deformity. Hardware is used to hold the bones in place.


An example of numerous exostosis growing off of the long bones of the leg. These bones compress nerves, deviate arteries, create bursas and catch on ligaments. One type of exostosis is pedunculated or stalk  like in appearance. These tumors are more prone to causing bursas and even to breaking. The other type of exostosis is sessile or mound like. This type when large is more likely to tether one side of the growth plate causing angular limb deformities and limb length inequalities.