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

• HMO (Hereditary Multiple Osteochondroma)

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

• Hereditary Multiple Osteochondromas, or HMOs (formerly called hereditary multiple exostoses), is a genetic condition in which people develop multiple benign (noncancerous) bone tumors that are covered by cartilage (called osteochondromas)
• The number and location of osteochondromas varies greatly among affected individuals. These tumors are not present at birth, but almost all affected people develop multiple osteochondromas by the time they are 12 years old
• Once the bones stop growing, the development of new osteochondromas also usually stops. Osteochondromas can cause abnormal growth of the arms, hands, and legs, which can lead to uneven limb lengths (limb length discrepancy) and short stature
• These tumors may cause pain, limit joint movement, and exert pressure on nerves, blood vessels, and surrounding tissues
• Osteochondromas are typically benign; however, researchers estimate that people with HMO have about a 1% lifetime risk of these tumors becoming a cancerous osteochondrosarcoma
• HMO is caused by mutations in the EXT1 and EXT2 genes and is inherited in an autosomal dominant pattern

(Source: Hereditary Multiple Osteochondromas; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

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

• Hereditary Multiple Osteochondromas is a rare congenital disorder, which occurs at a frequency of 1:50,000
• The presentation of symptoms may begin in childhood; most affected individuals are symptomatic by age 12
• Both males and females may be affected
• Although the condition may affect individuals worldwide, it is more common in some isolated populations. These include the Chamorro population in Guam (occurring at a frequency of 1:1,000) and Ojibway Indian population in Canada (1 in 77 individuals is affected)

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

• A positive family history may be an important risk factor, since Hereditary Multiple Osteochondromas is an inherited condition
• Currently, no other risk factors have been clearly identified for this condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s 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 Osteochondromas? (Etiology)

• Hereditary Multiple Osteochondromas is reportedly the result of genetic mutations involving the EXT1 and EXT2 genes
• The disorder is inherited in an autosomal dominant pattern

Autosomal dominant inheritance: 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 function 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 Osteochondromas?

The signs and symptoms of Hereditary Multiple Osteochondromas may include the following:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of the humerus 
• Abnormality of tibia morphology
• Failure to thrive
• Multiple exostoses

Frequently present symptoms in 30-79% of the cases:

• Abnormality of femur morphology
• Abnormality of the dentition
• Abnormality of the metaphysis
• Anteverted nares
• Aseptic necrosis 
• Bone pain 
• Cranial nerve paralysis 
• Genu valgum
• Hypoplasia of the ulna 
• Madelung deformity 
• Micromelia 
• Muscle weakness
• Radial bowing 
• Short stature

Occasionally present symptoms in 5-29% of the cases:

• Abnormal pericardium morphology 
• Abnormal pyramidal signs 
• Chondrosarcoma 
• Dilatation 
• Elbow dislocation
• Hemiplegia/hemiparesis 
• Osteoarthritis
• Osteolysis 
• Pelvic bone exostoses 
• Recurrent fractures
• Scoliosis
• Synostosis of joints

(Source: Hereditary Multiple Osteochondromas; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Hereditary Multiple Osteochondromas Diagnosed?

Hereditary Multiple Osteochondromas is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

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 Osteochondromas?

The complications of Hereditary Multiple Osteochondromas may include:

• Severe pain due to tumors
• Limited joint movement
• Tumor(s) exerting pressure on nearby tissue and nerves
• Tumors continuing to grow even after the bone growth has stopped
• Depression
• Transformation to cancerous osteochondrosarcoma (risk of approximately 1%)
• Metastasis of cancerous osteochondrosarcoma

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hereditary Multiple Osteochondromas Treated?

There is no cure for Hereditary Multiple Osteochondromas, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment methods may include:

• Surgery for complete excision of tumors, if there is severe pain and/or bone fracture associated with the condition, or if the tumors do not stop growing
• Surgical correction of limb abnormalities

How can Hereditary Multiple Osteochondromas be Prevented?

Currently, Hereditary Multiple Osteochondromas may not be preventable, since it is a genetic disorder.

• 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

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

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

• The prognosis of Hereditary Multiple Osteochondromas may vary among the affected individuals
• But, it is generally favorable, since most tumors cease growth once the bones have stopped growing (usually by adulthood)
• However, in individuals with malignant transformation, the outcome may be determined by the age of the individual, stage of cancer, the overall health of the affected individual, and his/her response to treatment

Additional and Relevant Useful Information for Hereditary Multiple Osteochondromas:

Hereditary Multiple Osteochondromas was previously referred to by the following names:

• Hereditary multiple exostoses
• Hereditary multiple exostosis

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/