FaCD Online Syndrome Fact Sheet

Last updated: 07 May 2008

Name: Hereditary Multiple Exostoses

Synonym: HME, Hereditary Exostoses, Multiple Osteochondromatosis, Multiple Cartilaginous Exostoses

Mode of Inheritance: AD

OMIM number: 133700  


EXT1, mapped to 8q24.11-q24.13
EXT2, mapped to 11p11-p12

Tumor features


Tumor features (possible)

bone, malignant fibrous histiocytoma of the


Clinical hallmarks are the development of multiple exostoses, osteochondromas, during childhood. No new lesions appear after closure of the growth plates, although after surgery, regrowth of old lesions may occur. The disorder usually affects the region around the epiphysis of the long bones.[1]. Patients with EXT2 gene mutations may be less severely affected than the other HME patients[2,3].

Malignant transformation of the osteochdromas into chondrosarcoma is one of the possible complications: estimates of life-time risk vary from 0.5 to 25 %[4;5], but a realistic estimate is probably 0.5-2 %[1;6]. Multiple chondrosarcomas may occur in a single patient[7]. Malignant fibrous histiocytoma of the bone has been reported in rare cases[8].

Hereditary multiple exostoses should be differentiated from metachondromatosis, which features exostoses, mainly of hand and feet, and long-bone and iliac crest enchondromas. The majority of these shows spontaneous regression. Other syndromes to consider are Ollier disease (enchondromatosis) and Muffucci syndrome (enchondromas and hemangiomas).[9].


Hereditary Multiple Exostoses Support Group, UK 18 1 08
The MHE Coalition 24 1 08


[1] Hennekam RCM. Syndrome of the month: Hereditary multiple exostoses. J Med Genet 1991; 28:262-266.
[2] J├Ąger 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. Journal of orthopaedic research 2007; 25(12):1541-51.
[3] Francannet C, Cohen-Tanugi A, Le Merrer M, Munnich A, Bonaventure J, Legeai-Mallet L. Genotype-phenotype correlation in hereditary multiple exostoses. Journal of medical genetics 2001; 38(7):430-4.
[4] Canella P, Gardini F, Boriani S. Exostosis: development, evolution and relationship to malignant degeneration. Ital J Orthop Traumatol 1981; 7(3):293-298.
[5] Solomon L. Hereditary multiple exostosis. Am J Hum Genet 1964; 16(3):351-363.
[6] Schmale GA, Conrad EU, Raskind WH. The natural history of hereditary multiple exostoses. J Bone Joint Surg Am 1994; 76A:986-992.
[7] Altay M, Bayrakci K, Yildiz Y, Erekul S, Saglik Y. Secondary chondrosarcoma in cartilage bone tumors: report of 32 patients. Journal of orthopaedic science 2007; 12(5):415-23.
[8] Picci P, Stilli S. Malignant fibrous histiocytoma arising from an exostosis in a patient affected by multiple exostoses. Ital J Orthop Traumatol 1982; 8(2):205-206.
[9] Pannier S, Legeai-Mallet L. Hereditary multiple exostoses and enchondromatosis. Best practice & research. Clinical rheumatology 2008; 22(1):45-54.