Hereditary multiple osteochondromas

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hereditary multiple osteochondromas is a condition in which people develop multiple noncancerous (benign) bone tumors called osteochondromas. These tumors are capped with a layer of cartilage, which is a soft tissue that makes up much of the skeleton during early development. The number of osteochondromas and the bones on which they are located vary greatly among affected individuals.

Osteochondromas can develop at any time between birth and adolescence; they stop forming in the teenage years when skeletal growth ends. Osteochondromas most often form at the end of the long bones of the arms and legs, but they can also occur on several other bones, including spinal bones (vertebrae) and flat bones such as the hips and shoulder blades.

Because hereditary multiple osteochondromas can disrupt bone growth, affected individuals may be shorter than others in their family (shortened stature). These problems with bone growth may not affect the right and left sides equally and can result in uneven limb lengths (limb length discrepancy).

Osteochondromas can cause mild curving of the spine (scoliosis), lower arms, or ankles. Abnormal development of the hip joints (hip dysplasia) can also occur. Affected individuals may develop joint disease early in life (premature osteoarthritis). These skeletal problems can lead to difficulty walking, pain, and general discomfort. People with multiple osteochondromas may also have a limited range of movement in their joints. Osteochondromas on vertebrae or ribs can be life-threatening if they put pressure on nerves, blood vessels, or the spinal cord, or if they interfere with lung function.

Osteochondromas are typically benign; however, these tumors can become malignant (cancerous). Researchers estimate that people with hereditary multiple osteochondromas have a 2 to 10 percent risk of developing cancerous osteochondromas (sarcomas) in their lifetime.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Changes in the EXT1 and EXT2 genes cause hereditary multiple osteochondromas. Genetic changes that cause disease are called pathogenic variants. The EXT1 and EXT2 genes provide instructions for producing the proteins exostosin-1 and exostosin-2, respectively. The two exostosin proteins bind together and form a complex found in a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, the exostosin-1 and exostosin-2 complex modifies a protein called heparan sulfate so it can be used by the cell. Heparan sulfate is involved in regulating a variety of body processes, including bone formation (ossification) and the growth and specialization (differentiation) of cartilage-forming cells called chondrocytes.

The pathogenic variants in the EXT1 or EXT2 gene that cause hereditary multiple osteochondromas cause cells to produce of an exostosin-1 or exostosin-2 protein that cannot process heparan sulfate correctly. A lack functional heparan sulfate likely disrupts the processes of ossification and chondrocyte differentiation and causes osteochondromas to form.

If this condition is caused by a pathogenic variant in the EXT1 gene, it is called hereditary multiple osteochondromas type 1. A pathogenic variant in the EXT2 gene causes hereditary multiple osteochondromas type 2. While both type 1 and type 2 involve multiple osteochondromas, pathogenic variants in the EXT1 gene likely account for 65 to 70 percent of all cases of hereditary multiple osteochondromas, and the severity of the symptoms seems to be greater in people with type 1 than in those with type 2.

Researchers estimate that about 10 to 15 percent of people with hereditary multiple osteochondromas do not have a pathogenic variant in either the EXT1 or the EXT2 gene. It is not known what causes hereditary multiple osteochondromas in these individuals.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 90 percent of individuals with hereditary multiple osteochondromas inherit a pathogenic variant from one affected parent. The remaining 10 percent of cases result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of hereditary multiple osteochondromas is estimated to be at least 1 in 50,000 to 100,000 individuals.

Osteochondromas account for 20 to 50 percent of benign bone tumors and 9 percent of all bone tumors. Hereditary multiple osteochondromas account for 15 percent of all cases of osteochondromas.

Which doctor should you see?

The suggested department for discussing Hereditary multiple osteochondromas is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hereditary multiple osteochondromas. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.