What is Hereditary multiple exostoses

TL;DR: Hereditary multiple exostoses (HME) is a rare genetic disorder characterized by the development of multiple benign bone tumors, known as osteochondromas, which typically grow near the growth plates of long bones. These growths can cause skeletal deformities, pain, and restricted movement, and they require long-term orthopedic monitoring to manage potential complications.

What is Hereditary multiple exostoses and how does it affect the body?

Hereditary multiple exostoses (HME) is a condition where the body develops multiple bony outgrowths capped with cartilage, called osteochondromas. These tumors most frequently occur in the long bones of the arms and legs, such as near the knees, ankles, wrists, and shoulders. Because these growths occur near the growth plates, they can interfere with normal bone development, leading to limb length discrepancies, bowed legs, or restricted joint mobility. While these tumors are almost always benign, their presence can cause pressure on surrounding nerves, blood vessels, or tendons, leading to chronic pain or numbness. Within the Hereditary multiple exostoses community at DiseaseMaps.org, 266 members have shared their experiences, highlighting how varied the impact can be from person to person.

What causes Hereditary multiple exostoses?

Hereditary multiple exostoses is primarily caused by mutations in the EXT1 or EXT2 genes. These genes provide instructions for producing proteins that help build heparan sulfate, a complex molecule essential for proper bone growth and cartilage development. When these genes are mutated, the signaling process that tells bone cells when to stop growing is disrupted, leading to the formation of the characteristic bony bumps. Because this is a genetic condition, it follows an autosomal dominant inheritance pattern, meaning an individual only needs one copy of the mutated gene from one parent to develop the disorder.

Who is typically affected by the condition?

Hereditary multiple exostoses is a rare condition with an estimated prevalence of approximately 1 in 50,000 individuals worldwide. While both males and females are affected, clinical reports suggest that males may experience more severe skeletal symptoms. The condition is usually diagnosed in early childhood, with the vast majority of patients showing clinical signs by the age of 12. Because Hereditary multiple exostoses is hereditary, family history is a key factor in identifying at-risk children shortly after birth.

Key facts and clinical characteristics

It is important to differentiate Hereditary multiple exostoses from solitary osteochondromas, which are much more common and do not have a genetic, hereditary basis. Key clinical features include:

• Multiple growths: Patients typically have two or more osteochondromas, whereas solitary osteochondroma involves only one.


• Skeletal involvement: Common sites include the distal femur, proximal tibia, and proximal humerus.


• Growth cessation: Most osteochondromas stop growing when the individual reaches skeletal maturity (typically late adolescence).


• Malignant transformation: While rare (estimated at 1% to 5%), there is a small risk that an osteochondroma can transform into a secondary chondrosarcoma, necessitating regular clinical surveillance.

Next steps

• Consult an orthopedic surgeon who specializes in pediatric bone disorders or limb deformity.


• Request a referral to a clinical geneticist to discuss genetic testing and family planning.


• Join the community at DiseaseMaps.org to connect with other families living with Hereditary multiple exostoses.


• Maintain a regular schedule of imaging (X-rays or MRIs) as recommended by your physician to monitor any changes in growth size or pain levels.

Medical disclaimer: This information is for educational purposes only and does not constitute professional medical advice, diagnosis, or treatment; always seek the advice of your physician regarding any medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Hereditary multiple exostoses


• Orphanet: Hereditary multiple exostoses (ORPHA:323)


• OMIM (Online Mendelian Inheritance in Man): Multiple Osteochondromas (#133700)


• The MHE Research Foundation: Patient education and clinical resources