What are the other Names for this Condition? (Also known as/Synonyms)

• Bessel-Hagen Disease
• Familial Exostoses
• HME (Hereditary Multiple Exostoses)

What is Hereditary Multiple Exostoses? (Definition/Background Information)

• Hereditary Multiple Exostoses (HME) is a familial condition that causes the development of numerous bone tumors at various locations in the body; any bone in the body may be affected by HME. These bony tumors are called ‘exostoses’
• Most individuals start developing these benign tumors when they reach the age of 12 years. These tumors usually occur during the growth phase of one’s life. As one becomes an adult, the growth of new tumors do not occur
• A majority of the cases are caused by genetic mutation involving the EXT1 and EXT2 genes. HME may be inherited as an autosomal dominant trait
• The signs and symptoms of Hereditary Multiple Exostoses include bone abnormalities and associated defects, such as uneven limbs, joint movement restriction, etc. It is estimated that around or less than 5% of the individuals with HME develop malignancy
• Defects in the bone may be corrected through physiotherapy, the use of prosthetics, and surgical intervention, depending upon the severity of the condition
• Most individuals with mild Hereditary Multiple Exostoses can lead relatively normal lives. However, the prognosis depends upon the number of bone tumors, its location, and whether the benign tumors have turned malignant

Who gets Hereditary Multiple Exostoses? (Age and Sex Distribution)

• Hereditary Multiple Exostoses is a rare disorder among the general population, with an incidence rate of 1 in 50,000
• It is a congenital condition, but the signs and symptoms of HME manifests around adolescence (over 95% of the time when the child reaches 12 years)
• There is no report of any gender bias; both males and females are affected
• All racial and ethnic groups are affected, although a higher incidence (1 in 1000) is noted in certain groups of people in countries such as Guam (the Chamorro group) and Canada (the Ojibway Indian tribe of Manitoba)

What are the Risk Factors for Hereditary Multiple Exostoses? (Predisposing Factors)

• Hereditary Multiple Exostoses is transmitted genetically from the parents to their offspring; hence, those with a family history of HME, are at high risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hereditary Multiple Exostoses? (Etiology)

• Hereditary Multiple Exostoses is a genetic disorder that is inherited in an autosomal dominant pattern
• In this disorder, there are genetic mutations in the EXT1 and EXT2 genes (causing Hereditary Multiple Exostoses Type 1 and Hereditary Multiple Exostoses Type 2 respectively), which is responsible for the production of exostosin proteins
• The exostosin proteins play a role in the formation of the heparin sulfate protein, which is an essential component for several bodily processes. These mutated proteins work within the golgi apparatus of the cell to regulate bone health
• It is researched that a poorly-produced heparin sulfate causes the various signs and symptoms associated with HME, although the relation between the two is unclear
• However, there are exceptions to the above such as:
  • In nearly 1 in 7 cases, no abnormal mutations on EXT1 and EXT2 genes are observed
  • Also, some cases of HME are inherited as an autosomal recessive trait
  • Some cases have been identified where there is no family history of the disorder, but genetic mutations causing HME is seen

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Hereditary Multiple Exostoses?

The signs and symptoms of Hereditary Multiple Exostoses are mostly the result of multiple bone tumors that may form on any bone (limbs, spinal cord, etc.) of the body. These may include:

• Skeletal abnormalities due to disruption of bone growth, causing short stature
• Restricted joint movement, pain in the joints
• Discrepancy in the length of the right and left arm or leg, due to bone growth being affected
• The spinal cord may also be affected

How is Hereditary Multiple Exostoses Diagnosed?

Diagnostic tests that are performed for Hereditary Multiple Exostoses include:

• Complete physical examination with evaluation of medical history
• Radiographic exam (skeletal survey)
• Genetic testing and analysis
• Prenatal exams include amniocentesis and chorionic villus sampling to detect any abnormal mutations

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hereditary Multiple Exostoses?

The complications due to Hereditary Multiple Exostoses may include:

• Extreme pain, nerve damage, and the presence of weak bones
• Formation of malignant bone tumors called chondrosarcomas; the benign tumors can transform to form cancerous tumors. However, this is not very common for only between 0.5% to 5% of the cases result in such a malignant transformation
• Recurrence of the exostoses after surgery; in 20-50% of the cases recurrence is seen
• Damage of vital nerves, blood vessels, and surrounding structures during surgery to remove the tumor
• During pregnancy, pelvic bone tumors can cause complications during delivery, and hence, a C-section may be required

How is Hereditary Multiple Exostoses Treated?

Hereditary Multiple Exostoses is an incurable condition. An individualized treatment is planned and provided to improve the quality of life; based on the specific conditions/complications that are present:

• Some individuals manage their life despite the presence of the multiple lesions, and do not let it interfere with their life. They cope with their difficulties and slightly restricted motion range, by learning to adapt to any situation; thus not requiring any treatment or making do with minimal treatment
• Where bone tumors are painful, appear visually as inflamed lesions, causes severely restricted motion, or the growing bones deform or arch - surgical intervention is required
• But, due to the high recurrence rate, an individual may have to undergo multiple surgeries during their lifetime
• Post-surgical excision, bone defects may have to be corrected by using braces, physiotherapy, and even orthopedic invasive techniques
• The pain may be managed using medications; also, it is advisable to avoid any physical activities that tend to increase pain

How can Hereditary Multiple Exostoses be Prevented?

• Currently, there are no specific methods or guidelines to prevent Hereditary Multiple Exostoses, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Hereditary Multiple Exostoses
• Regular medical screening at periodic intervals with scans and physical examinations are mandatory; due to its slight metastasizing potential but high chance of recurrence. Often several decades of active vigilance is necessary

What is the Prognosis of Hereditary Multiple Exostoses? (Outcomes/Resolutions)

• Children with Hereditary Multiple Exostoses may have to endure difficult and stressful periods at home and school. However, with proper encouragement and supportive care, they can learn to cope with the condition and physically adapt to their environment
• In case limited motion and pain severely hamper the quality of life, surgical procedures and orthopedic therapies are available to correct certain bone anomalies
• Less than 5% of exostoses turn malignant, and in such cases, the prognosis could be grim

Additional and Relevant Useful Information for Hereditary Multiple Exostoses:

There are 3 kinds of malignant bone tumors - osteosarcoma, chondrosarcoma, and Ewing’s sarcoma.