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 . 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 , 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 . 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 .
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 . 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 . Acetabular osteochondromas can be treated surgically, but there is a danger of avascular necrosis . 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 . 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. This happens mainly in adults, especially older adults, in whom increased pain and enlargement of osteochondromas are the most likely presenting symptoms . Chondrosarcoma is diagnosed in 0.5-20% of HMO patients, the lower values being accepted by most authors .
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 . 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 . 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 .
Entire Body System
An unusual cause of subacromial pain was observed in a 32-year-old woman with multiple exostoses. The pain was the direct result of the mechanical impingement syndrome from these exostoses. [ncbi.nlm.nih.gov]
Neuropathic pain was reported by 13% of respondents. QOL inversely correlated with pain severity. 16 Despite usually worsening FOP, surgery is sometimes required. [ajmc.com]
At 1.5 years after surgery, the patient had a satisfactory outcome with a fully functional, pain-free forearm in a fixed, neutral position. [insights.ovid.com]
- Short Stature
Hereditary multiple exostoses is an autosomal dominant disorder that is characterized by short stature and multiple, benign bone tumours. [ncbi.nlm.nih.gov]
Impaired body growth (symmetrical and asymmetrical) is common and results in: [ 6 ] Short stature. Limb-length discrepancies. Valgus deformities of the knee and ankle. Asymmetry of the pectoral and pelvic girdles. [patient.info]
The most common deformities include short stature, limb-length discrepancies, valgus deformities of the knee and ankle, asymmetry of the pectoral and pelvic girdles, bowing of the radius with ulnar deviation of the wrist, and subluxation of the radiocapitellar [doi.org]
- Swelling of the Finger
Case Report We present a case of an 18-year-old male who suffered since his childhood from multiple small swellings affecting the fingers of his both hands. [journalmsr.com]
- Bone Disorder
Hereditary multiple exostoses (HME) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors. [ncbi.nlm.nih.gov]
MHE is a genetic bone disorder in which benign, cartilage-capped tumors (Exostoses or Osteochondromas) grow from the growth plate of long bones or from the surface of flat bones throughout the body. [globalgenes.org]
Fibrodysplasia ossificans progressiva (FOP) and multiple osteochondromas (MO) are 2 rare and debilitating bone disorders that can have a serious impact on the quality of life (QOL) of those individuals who are affected. [ajmc.com]
Introduction Hereditary multiple exostoses (HME or MHE ), also known as multiple osteochondromatosis (MO) or diaphyseal aclasis is a genetic bone disorder in which cartilage outgrowths called exostoses or ostechondromas form next to the growth plate of [flipper.diff.org]
- Genu Valgum
[…] 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]
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]
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]
Simultaneous treatment for patellar instability and genu valgum in skeletally immature patients: a preliminary study. Parikh, SN; Redman, C; Gopinathan, NR. Journal of Pediatric Orthopaedics. Part B. 2019 ; 28 : 132-138. [cincinnatichildrens.org]
- 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]
The main presenting features were painless progressively increasing bony swellings in both upper and lower limbs. One of them had pressure symptoms which necessitated surgical excision of the symptomatic exostosis. [jmscr.igmpublication.org]
She presented with afebrile seizures, learning impairment, stunted growth, macrocephaly and multiple bony swellings. Similar bony swellings were observed in the mother and the sibling of the index case. [panafrican-med-journal.com]
Physical examination revealed multiple, hard, immobile bony swellings over the dorsum of the left hand involving the 3 rd and 5 th metacarpal bones. [journalmsr.com]
- Joint Deformity
deformities such as distal radius hemiepiphysiodesis and medial distal tibial hemiepiphysiodesis.   Nevertheless, there is little evidence to support the ongoing pediatric orthopedic practice in hereditary multiple osteochondromas. [en.wikipedia.org]
deformities, and correction of limb-length discrepancies; in growing children, epiphysiodesis can be used for the management of limb-length discrepancies. 7 Complete removal of symptomatic exostoses is advocated to avoid recurrence and malignancy. 7 [healio.com]
The exostoses of metachondromatosis occur predominantly in the digits and, unlike those of hereditary multiple exostosis, point toward the nearby joint and do not cause shortening or bowing of the long bone, joint deformity, or subluxation. [slideshare.net]
- Leg Length Inequality
length inequality may be severe enough to require equalization procedures in half of the individuals; - Ulna in MED: - shortening is the major problem. - distal ulna contributes more to total bone length than does distal radius and therefore is more [wheelessonline.com]
Hereditary Multiple Exostoses ... nerves, and leg-length inequalities. [slideshare.net]
Angular deformities, leg-length inequalities and pain resulting from inflammation of skin, tendons or nerves often require surgery. The flat bones like iliac and scapula are less frequently involved. [wjgnet.com]
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 .
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 , although magnetic resonance imaging is thought to be optimal for measuring cap thickness . 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 . Several investigators advocate instituting screening programs in adults harboring osteochondromas for the early detection of malignant transformation   .
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]
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]
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]
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]
Etiology is multifactorial and not well established. Tori and exostoses have been associated. Oct 05, 2010 · Er:YAG laser treatment of post-estraction exostosis. [f2a.vamagazin.com]
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 exostoses: identification of "protective" and "risk" factors. 4 Pedrini E...Sangiorgi L 22258776 2011 31 Use of the eight-Plate for angular correction of knee deformities due to idiopathic and pathologic physis: initiating treatment according to etiology [malacards.org]
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]
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]
Clinical, radiological, immunological and epidemiological parameters play important role in diagnosis of Diaphyseal aclasis [ 10 - 13 ]. Osteochondromatosis is the most frequent benign bone tumor of the skeletal system [ 10, 14 - 19 ]. [omicsonline.org]
Controversy exists as to the pathophysiology of vascular complications. [scvs.org]
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]
Symptoms are more likely to be severe if the mutation is on the ext1 gene rather than ext2 or ext3 ; ext1 is also the most commonly affected gene in patients of this disorder.  Pathophysiology [ edit ] It is characterized by the growth of cartilage-capped [en.wikipedia.org]
Since 1993, advances have been noted in knowledge of the pathophysiology of this disease, in particular with the discovery of the mutation of EXT genes, found in 80% of multiple exostosis disease. [rarediseasesjournal.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]
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. [doi.org]
In the rare cases of malignant transformation, radical surgery is important for the prognosis and to prevent the progression of the lesions. If the complete removal is not possible, the therapy of choice is adjuvant radiotherapy. [sciedu.ca]
- 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.
- 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.
- 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.
- Bovée JV. Multiple osteochondromas. Orphanet J Rare Dis. 2008 Feb; 13;3:3.
- Woodside CJ, Ganey T, Gaston RG. Multiple osteochondroma of the hand: initial and long-term follow-up study. HAND. 2015;10:616-620.
- Malagon V. Development of hip dysplasia in hereditary multiple exostosis. J Pediatr Orthop. 2001;21:205–211.
- 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.
- 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.
- Hennekam RC: Hereditary multiple exostoses. J Med Genet. 1991;28:262-266.
- 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.
- 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.
- 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.
- Park YK, Yang MH, Ryu KN, Chung DW. Dedifferentiated chondrosarcoma arising in an osteochondroma. Skeletal Radiol. 1995 Nov;24(8):617-619.
- Shah ZK, Peh WC, Wong Y, Shek TW, Davies AM. Sarcomatous transformation in diaphyseal aclasis. Australas Radiol. 2007 Apr;51(2):110-119.
- 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.