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Hereditary Multiple Exostoses

Multiple Osteochondromas

Hereditary multiple exostoses - or hereditary multiple osteochondromas (HMOs) - are benign bone tumors. Many patients lead active, normal lives, but the condition is often painful and associated with complications that affect stature and mobility. The most serious complication is the malignant transformation of osteochondromas into sarcomas.


Osteochondroma is a bony outgrowth that has a cap of cartilage [1]. It can be sessile (broad at its base) or pedunculated. The latter form is more likely to cause problems. The characteristic feature of osteochondroma is the continuity of both the cortex and the medullary bone between the growth and the bone of origin. The most frequent sites of growth are from long bones such as the femur, tibia (around the region of the knee), nd the fibula, the radius and the ulna in the arm. It can also occur in the hand and on the surface of some flat bones (pelvis and scapula).

About 85% of patients with osteochondromas have solitary growths without a family history while the remaining 15% of the patients present with HMO [2], inherited in an autosomal dominant manner. Affected individuals usually lack signs of the disease at birth, but almost all are diagnosed by the age of 12. By the age of 3, the problem is identified in half of the patients [3]. Osteochondromas stop growing after the usual time of the closure of growth plates. The number of osteochondromas per person is variable – even in patients within the same family – with mean values of 15-18 [4].

Although the lives of the majority of patients are not disrupted by the disease, osteochondromas can be associated with a variety of complications depending on the number, location, and size of the tumors. Stature is shortened, though still in the normal range in about a quarter of the patients. Pain is a problem for most of the affected individuals, caused by the osteochondromas pressing or impinging tendons and muscles, sometimes restricting movement in joints, or causing bursitis.

Osteochondromas can also impede the growth of bones and result in bone deformities. For example, osteochondromas may lead to shortening of the ulna, which can bring about the curving of the radius, or the dislocation of its head. The bones most frequently involved in hand deformities are the index and small fingers [5]. Osteochondroma occurs in about a quarter of patients at the proximal metaphysis of the femur and results in coxa valga and in deformities in the acetabular cavity [6]. Acetabular osteochondromas can be treated surgically, but there is a danger of avascular necrosis [7]. The knee area is also a common place for problems, with 70% of patients having knee osteochondromas. Genu valgum occurs in about a third of the patients [8]. Pedunculated osteochondromas carry a risk of fracture in the region of the stalk [4].

Malignant transformation of the osteochondroma to chondrosarcoma is the most serious consequence of the disease. This happens mainly in adults, especially older adults, in whom increased pain and enlargement of osteochondromas are the most likely presenting symptoms [9]. Chondrosarcoma is diagnosed in 0.5-20% of HMO patients, the lower values being accepted by most authors [10].

Mutations in two genes are associated with the appearance of osteochondromas: Exostosin-1 and Exostosin-2 (EXT1 and EXT2), both coding for glycosyltransferases whose function is the polymerization of heparan sulfate chains [11]. These enzymes are thought to act as tumor suppressors; they have a role in the efficient functioning of growth factors and signaling molecules that regulate the division and differentiation of chondrocytes at the growth plate [4]. Patients with mutations in the EXT1 gene present with more severe symptoms, - such as more functional complications and increased risk of chondrosarcoma, - than those with EXT2 mutations [12].

Genu Valgum
  • Genu valgum occurs in about a third of the patients. Pedunculated osteochondromas carry a risk of fracture in the region of the stalk. Malignant transformation of the osteochondroma to chondrosarcoma is the most serious consequence of the disease.[symptoma.com]
  • For example, genu valgum (knock knees), ankle valgus, ulnar bowing and shortening, and radial head subluxation are encountered. The majority of affected individuals have clinically manifest osteochondromas around the knee.[en.wikipedia.org]
  • […] hemiepiphysis may improve wrist alignment as well as improving supination and pronation; - ulnar lengthening: - Knee Joint in MED: - leg length inequality may require equalization procedures in 50%; - fibular involvement by osteochondroma may cause: genu[wheelessonline.com]
  • Genu valgum and ankle valgus may be seen.[orthopaedicsone.com]
Bony Swelling
  • The main presenting features were painless progressively increasing bony swellings in both upper and lower limbs, with forearm deformity and ulnar deviation of the wrist.[ncbi.nlm.nih.gov]
Bony Swelling
  • The main presenting features were painless progressively increasing bony swellings in both upper and lower limbs, with forearm deformity and ulnar deviation of the wrist.[ncbi.nlm.nih.gov]
Morning Stiffness
  • At the age of 40 years, pain in the lower back associated with morning stiffness lasting about an hour and improving with exercise began. His son also has hereditary multiple exostoses but has no sign of AS. HME is an autosomal dominant disorder.[ncbi.nlm.nih.gov]
  • The posterior thoracic vertebral body appears to be a novel origin for an exostosis causing myelopathy.[ncbi.nlm.nih.gov]
  • Spinal osteochondroma is a rare but recognized cause of myelopathy. Brown-Séquard syndrome is a form of severe myelopathy characterized by a clinical picture of hemisection of the spinal cord.[ncbi.nlm.nih.gov]
  • Substantiated myelopathy in hereditary multiple exostoses is very rare. A few cases have been reported previously.[ncbi.nlm.nih.gov]
  • A 58-year-old woman with hereditary multiple exostoses had slowly progressive myelopathy due to a vertebral exostosis that compressed the spinal cord at T1-2. She did not show skeletal deformities, but had numerous palpable long-bone exostoses.[ncbi.nlm.nih.gov]
  • A case of hereditary multiple exostoses with acute cervical myelopathy, tetraplegia, and apnea is reported. Neurological complications as a result of osteochondromas in hereditary multiple exostoses are rare.[ncbi.nlm.nih.gov]
Spastic Quadriplegia
  • We report a case of a 12-year-old girl with an exostosis in the cervical spine (C5), which caused a spastic quadriplegia.[ncbi.nlm.nih.gov]


After a skeletal outgrowth is discovered, the physician obtains patient and family histories and assesses the outgrowth radiologically and possibly histologically.

Conventional X-ray imagery is often adequate to characterize the lesions, which appear with clear margins and often with scattered calcifications. Important signs that distinguish sarcomatous growths from osteochondromas are enlargement of the tumor and irregular margins [13].

Computerized tomography is considered an efficient tool for detecting osteochondromas that are located in areas where they are not easily visible, for example, the spine.

Ultrasound and angiography are used for diagnosing vascular problems, such as thrombosis. Ultrasound is also efficient in determining the thickness of the cartilaginous cap on the growth [2], although magnetic resonance imaging is thought to be optimal for measuring cap thickness [14]. A cap thickness greater than 2-3 cm is considered a strong indication of chondrosarcoma.

Magnetic resonance imaging (MRI) is also used for differential diagnosis and for detecting vascular complications.

High metabolic activity in malignant growth can be detected by radionucleotide uptake in bone scans. Fluorodeoxyglucose-positron emission tomography scans can also be used to detect malignant transformation [15]. Several investigators advocate instituting screening programs in adults harboring osteochondromas for the early detection of malignant transformation [1] [3] [12].

  • AS has a remarkably strong association with the histocompatibility antigen HLA-B27. Owing to the different genetic mechanisms, it is not possible to differentiate between coincidence and association.[ncbi.nlm.nih.gov]
  • Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthrit Rheum. 1998; 41 (1): 58-67 2. Wilkinson M, Bywaters EGL.[iranjradiol.com]


  • Most patients needed no treatment. Surgical treatment was often directed to remove symptomatic exostoses, particularly those of suspected malignancy degeneration, and correction of skeletal deformities.[ncbi.nlm.nih.gov]
  • Treatment of both forearms resulted in functional, painless extremities at 3- and 14-year follow-up.[ncbi.nlm.nih.gov]
  • This was a very rare situation, and the result validated the treatment used.[ncbi.nlm.nih.gov]
  • Treatment of mouse embryo limb mesenchymal micromass cultures with exogenous heparanase greatly stimulated chondrogenesis and bone morphogenetic protein signaling as revealed by Smad1/5/8 phosphorylation.[ncbi.nlm.nih.gov]
  • To the authors' knowledge, few reports have been published in the English literature of using total knee arthroplasty and total hip arthroplasty for the treatment of hereditary multiple exostoses.[ncbi.nlm.nih.gov]


  • What patient characteristics are associated with better prognosis? What disease characteristics are associated with better prognosis? We searched the literature using three major databases with no publication date restrictions.[ncbi.nlm.nih.gov]
  • What patient characteristics are associated with better prognosis? What disease characteristics are associated with better prognosis? Methods : We searched the literature using three major databases with no publication date restrictions.[doi.org]
  • Prompt diagnosis and surgical excision affords the best prognosis for these patients who have spinal cord compression secondary to intracanalicular osteochondroma.[ncbi.nlm.nih.gov]
  • Prompt diagnosis and surgical excision provide the best prognosis.[ncbi.nlm.nih.gov]
  • Prognosis The prognosis depends on the development of complications. Spontaneous resolution of osteochondromas during childhood and puberty is rare but has been described.[patient.info]


  • Genomic deletions and duplications play an important role in the etiology of human disease. Versatile tests are required to detect these rearrangements, both in research and diagnostic settings.[ncbi.nlm.nih.gov]
  • Hereditary Multiple Exostoses: One Center’s Experience and Review of Etiology. Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study.[wheelessonline.com]
  • Hereditary multiple exostoses: one center's experience and review of etiology. Clin Orthop Relat Res. 2002 Aug;(401):49-59. Porter DE, Lonie L, Fraser M, Dobson-Stone C, Porter JR, Monaco AP, Simpson AH.[ghr.nlm.nih.gov]
  • .: hereditary Hereditary multiple exostoses: one center’s experience and review of etiology. Clin Orthop Rel Res 401:49–59, 2002. CrossRef Google Scholar 21.[link.springer.com]
  • (Etiology) Hereditary Multiple Exostoses is a genetic disorder that is inherited in an autosomal dominant pattern In this disorder, there are genetic mutations in the EXT1 and EXT2 genes (causing Hereditary Multiple Exostoses Type 1 and Hereditary Multiple[dovemed.com]


  • This study investigated the epidemiology, clinical presentations, pathogenetic features and treatment strategies of HME in mainland China.[ncbi.nlm.nih.gov]
  • Epidemiology Affects 2 per 100,000 population. [ 2 ] More frequently found in Caucasians than in other races. Risk factors Inheritance is autosomal dominant, with near-complete penetrance.[patient.info]
  • Multiple osteochondromas, 2008 Hereditary multiple exostoses, 1991 Manifestation of HME, 2005 Epidemiology The prevalence of HME is estimated at 1:50000 people within the general population and seems to be higher in males (male to female ratio 1,5:1).[flipper.diff.org]
Sex distribution
Age distribution


  • Pathophysiology [ edit ] Osteochondroma is continuous with underlying medullary and cortical bone. A hyaline cartilage cap involutes after reaching skeletal maturity. The solitary form is the only benign neoplasm associated with radiation.[en.wikibooks.org]
  • The present study identified a novel disease-causing EXT1 mutation exclusively in all patients in a Chinese pedigree with HME, which not only highlights the critical pathophysiological role of the EXT1 gene in HME, but also supports the high value of[spandidos-publications.com]
  • Discussion The pathophysiology of hereditary multiple exostoses is attributed to mutations in the exostosin (EXT)1, EXT2, and EXT3 genes. 4 Exostosin 1 and EXT2 code for transmembrane glycoproteins that help regulate cell surface heparin sulfate proteoglycans[healio.com]


  • Careful analysis of the 5 cases suggested to us that patients with HME should have a systematic spinal imaging screening, in order to prevent rapid neurological decompensation. A minimal risk surgical procedure can be performed at a time of election.[ncbi.nlm.nih.gov]
  • A better knowledge of this disease could have prevented this neurological complication.[ncbi.nlm.nih.gov]
  • For certain deformities, surgery can prevent progression and provide correction. Patients with hereditary multiple exostosis have a slight risk of sarcomatous transformation of the cartilaginous portion of the exostosis.[ncbi.nlm.nih.gov]
  • We should consider guided growth for patients with lower HEA to prevent significant coxa valga deformity with close follow-up.[ncbi.nlm.nih.gov]



  1. Beltrami G, Ristori G, Scoccianti G, Tamburini A, Capanna R. Hereditary Multiple Exostoses: a review of clinical appearance and metabolic pattern. Clin Cases Miner Bone Metab. 2016 May-Aug;13(2):110-118.
  2. Kitsoulis P, Galani V, Stefanaki K, et al. Osteochondromas: review of the clinical, radiological and pathological features. In Vivo. 2008 Sep-Oct;22(5):633-646.
  3. Sonne-Holm E, Wong C, Sonne-Holm S. Multiple cartilaginous exostoses and development of chondrosarcomas--a systematic review. Dan Med J. 2014 Sep;61(9):A4895.
  4. Bovée JV. Multiple osteochondromas. Orphanet J Rare Dis. 2008 Feb; 13;3:3.
  5. Woodside CJ, Ganey T, Gaston RG. Multiple osteochondroma of the hand: initial and long-term follow-up study. HAND. 2015;10:616-620.
  6. Malagon V. Development of hip dysplasia in hereditary multiple exostosis. J Pediatr Orthop. 2001;21:205–211.
  7. Ofiram E, Porat S. Progressive subluxation of the hip joint in a child with hereditary multiple exostosis. J Pediatr Orthop B. 2004;13:371–373.
  8. Clement ND, Porter DE. Can deformity of the knee and longitudinal growth of the leg be predicted in patients with hereditary multiple exostoses? A cross-sectional study. The Knee. 2014;21:299-303.
  9. Hennekam RC: Hereditary multiple exostoses. J Med Genet. 1991;28:262-266.
  10. Legeai-Mallet L, Munnich A, Maroteaux P, Le Merrer M. Incomplete penetrance and expressivity skewing in hereditary multiple exostoses. Clin Genet. 1997 Jul;52(1):12-16.
  11. Jennes I, Pedrini E, Zuntini M, et al. Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb). Hum Mutat. 2009;30:1620–1627.
  12. Porter DE, Lonie L, Fraser M, et al. Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study. J Bone Joint Surg Br. 2004 Sep;86(7):1041-1046.
  13. Park YK, Yang MH, Ryu KN, Chung DW. Dedifferentiated chondrosarcoma arising in an osteochondroma. Skeletal Radiol. 1995 Nov;24(8):617-619.
  14. Shah ZK, Peh WC, Wong Y, Shek TW, Davies AM. Sarcomatous transformation in diaphyseal aclasis. Australas Radiol. 2007 Apr;51(2):110-119.
  15. Aoki J, Watanabe H, Shinozaki T, Tokunaga M, Inoue T, Endo K. FDG-PET in differential diagnosis and grading of chondrosarcomas. J Comput Assist Tomogr. 1999;23:603–608.

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Last updated: 2019-07-11 20:14