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.

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.

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.

Genetic Testing Information

• Genetic Testing Registry: Exostoses, multiple, type 2
• Genetic Testing Registry: Multiple congenital exostosis

Genetic and Rare Diseases Information Center

• Multiple osteochondromas

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• EXOSTOSES, MULTIPLE, TYPE I; EXT1
• EXOSTOSES, MULTIPLE, TYPE II; EXT2

Scientific Articles on PubMed

• PubMed

• Alvarez CM, De Vera MA, Heslip TR, Casey B. Evaluation of the anatomic burden of patients with hereditary multiple exostoses. Clin Orthop Relat Res. 2007 Sep;462:73-9. doi: 10.1097/BLO.0b013e3181334b51. Citation on PubMed
• Bovee JV. Multiple osteochondromas. Orphanet J Rare Dis. 2008 Feb 13;3:3. doi: 10.1186/1750-1172-3-3. Citation on PubMed
• Jager M, Westhoff B, Portier S, Leube B, Hardt K, Royer-Pokora B, Gossheger G, Krauspe R. Clinical outcome and genotype in patients with hereditary multiple exostoses. J Orthop Res. 2007 Dec;25(12):1541-51. doi: 10.1002/jor.20479. Citation on PubMed
• Komura S, Matsumoto K, Hirakawa A, Akiyama H. Natural History and Characteristics of Hand Exostoses in Multiple Hereditary Exostoses. J Hand Surg Am. 2021 Sep;46(9):815.e1-815.e12. doi: 10.1016/j.jhsa.2020.12.011. Epub 2021 Feb 26. Citation on PubMed
• Legler J, Benaroch LR, Pirshahid AA, Serhan O, Cheng D, Bartley D, Carey T, Rasoulinejad P, Singh S, Thornley P. Rate of Spinal Osteochondromas Diagnosed in Pediatric Patients With Hereditary Multiple Osteochondromas: A Systematic Review and Meta-Analysis. J Pediatr Orthop. 2025 Sep 1;45(8):e718-e723. doi: 10.1097/BPO.0000000000002975. Epub 2025 Apr 23. Citation on PubMed
• Pedrini E, Jennes I, Tremosini M, Milanesi A, Mordenti M, Parra A, Sgariglia F, Zuntini M, Campanacci L, Fabbri N, Pignotti E, Wuyts W, Sangiorgi L. Genotype-phenotype correlation study in 529 patients with multiple hereditary exostoses: identification of "protective" and "risk" factors. J Bone Joint Surg Am. 2011 Dec 21;93(24):2294-302. doi: 10.2106/JBJS.J.00949. Citation on PubMed
• Pei Y, Wang Y, Huang W, Hu B, Huang D, Zhou Y, Su P. Novel mutations of EXT1 and EXT2 genes among families and sporadic cases with multiple exostoses. Genet Test Mol Biomarkers. 2010 Dec;14(6):865-72. doi: 10.1089/gtmb.2010.0040. Epub 2010 Nov 1. Citation on PubMed
• Petersen RB, Buch CD, Faergemann C, Nymark T. Bone deformities with hereditary multiple osteochondromas. Dan Med J. 2025 Apr 29;72(5):A11230696. doi: 10.61409/A11230696. Citation on PubMed
• Sefcik R, Earl D. Hereditary Multiple Osteochondromas. 2000 Aug 3 [updated 2026 Jan 29]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1235/ Citation on PubMed
• Tepelenis K, Papathanakos G, Kitsouli A, Troupis T, Barbouti A, Vlachos K, Kanavaros P, Kitsoulis P. Osteochondromas: An Updated Review of Epidemiology, Pathogenesis, Clinical Presentation, Radiological Features and Treatment Options. In Vivo. 2021 Mar-Apr;35(2):681-691. doi: 10.21873/invivo.12308. Citation on PubMed