Multiple Hereditary Exostoses. Clinical problems and therapeutic options

Multiple Hereditary Exostoses. Clinical problems and therapeutic options

GENETIC DISORDERS Multiple Hereditary Exostoses. Clinical problems and therapeutic options chondrosarcoma is a major complication in adult patients,...

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GENETIC DISORDERS

Multiple Hereditary Exostoses. Clinical problems and therapeutic options

chondrosarcoma is a major complication in adult patients, with a reported incidence of approximately 3e6%.6e9 In this paper, an overview is provided concerning the most common clinical problems encountered in MHE and treatment options are discussed.

SJ Ham

Pathology Osteochondroma Osteochondroma is defined by the WHO as a cartilage-capped bony outgrowth, which is broad-based (sessile) or stemmed (pedunculated) and is made up of cortex and a marrow cavity both continuous with the host bone. In the long bones of the extremities, osteochondromas develop in the metaphysis, and grow away from the ankle joint and the epiphyseal plate of origin. The pedunculated osteochondromas are always directed away from the growth plate and the joint. In broad-based osteochondromas it can be difficult to differentiate the tumour from the normal underlying bone. Osteochondromas develop and increase in number and size during childhood until closure of the growth plates. In MHE, the osteochondromas are often highly irregular and can become extremely large (Figure 1). The most common location for osteochondromas is at the side of the most active growth plate of a long bone which contributes most to the longitudinal growth. The most common sites are the proximal humerus, distal radius, distal ulna, proximal tibia, and distal femur. The axial skeleton, the pelvis, ribs and scapula are also often affected. Osteochondromas are not located in the facial bones, and rarely in carpal and tarsal bones. Following excision of osteochondromas in children, local recurrence may occur. This can be due to incomplete excision or the development of a new osteochondroma at the same location. Spontaneous regression of osteochondromas has been documented in single cases during childhood and adolescence.

Abstract Multiple Hereditary Exostoses (MHE) is a rare autosomal dominant disorder characterized by the presence of multiple osteochondromas. Patients often present with growth disturbances and angular deformities of the long bones, and a limited range of motion of the joints. In adults, the risk of malignant transformation of osteochondroma into chondrosarcoma exists, with an estimated incidence of 3e6%. In addition to the physical deformities, pain is a significant problem for patients with MHE and the disease has a profound negative influence on activities of daily living, occupation and school performance. In the treatment of patients with MHE, knowledge about the various disorders encountered and the natural course of the disease, as well as appropriate timing of interventions are essential. Surgical treatment may not only include the excision of osteochondromas but also limb reconstruction procedures to correct deformities. During childhood, however, this may be limited to procedures such as hemiepiphysiodesis for valgus deformity of the knee and ankle to prevent more extensive surgery at older age. Furthermore, early recognition of malignant degeneration of osteochondroma and the immediate treatment of chondrosarcoma are of the utmost importance for patient survival. Therefore, periodic screening in children as well as adults is highly recommended.

Keywords Multiple hereditary exostoses; osteochondroma; growth disturbances; forearm deformity; malignant transformation

Prevalence MHE is relatively rare with an estimated prevalence in Caucasians of 1 per 50 000 individuals.6 The true prevalence, however, is not known because individuals without complaints or with only mild asymptomatic lesions are often not diagnosed as MHE. Higher prevalence of 50 and 655 per 50 000 individuals, respectively, have been found in isolated communities.10,11 Obviously, an hereditary factor played a crucial role in this. In our institution’s database, we currently have 450 patients with MHE. As a substantial number of other individuals and families in the Netherlands are known to be treated at other hospitals, and the population in the Netherlands is known to be seventeen million, this means that the prevalence must be higher in our country. In approximately 70% of affected individuals, a family history of MHE exists, whereas 30% of the cases are spontaneous genetic mutations.8 The aspect, size and number of osteochondromas as well as the severity of skeletal deformities often varies between affected individuals and even members of the same family.12 In most cases, one side is predominantly affected within a person or family. Patients and families with EXT1 mutation seem to have a more severe phenotype than EXT2 patients.4,9 In approximately 50% of individuals, multiple osteochondromas are initially diagnosed before 3.5 years of age. In more

Introduction Multiple Hereditary Exostoses (MHE), also known as multiple osteochondromas (osteochondromata), is a monogenetic, autosomal dominant disorder characterized by the presence of multiple osteochondromas. It is caused by loss of function mutations in either exostosin-1 (EXT1) (8q23-q24) or exostosin-2 (EXT2) (11p11-p12).1e3 EXT1 and EXT2 mutations are found in approximately 90% of all cases.4 Although MHE may be asymptomatic, in general a wide spectrum of clinical manifestations is found in patients with this disorder. The most common clinical problems associated with MHE include pain and functional impairment due to compression by osteochondromas on the surrounding soft tissues or due to mechanical obstruction caused by the size of the osteochondromas.5e8 Additionally, limb deformities are present in a considerable number of patients. Malignant degeneration of osteochondroma into

SJ Ham MD PhD Consultant Orthopaedic Surgeon in Department of Orthopaedic Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. Conflict of interest: none.

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neurovascular structures and joints. T2-weighted series with fat suppression are of importance to measure the size of the cartilaginous cap and to visualize an overlying bursa. Osteochondromatous growth takes place in the cartilaginous cap only during childhood. Pain, subjective growth of an osteochondroma in adulthood, and a cartilaginous cap more than 1e2 cm in size should arouse suspicion of malignant transformation of osteochondroma into a chondrosarcoma.13,14 Bone scintigraphy can be used to detect locations at risk for malignant transformation, but has a low specificity. Whole-body MRI could be a useful screening modality to rule out or detect malignant degeneration in an early phase.

Clinical problems MHE can lead to a variety of clinical symptoms and disorders as detailed in Table 1. However, MHE is not only limited to physical complaints and inconveniences, but also has a profound effect on daily life. From the literature, little is known with regard to the general health status of patients with MHE or the severity of pain and loss of function, and how MHE influences the activities of daily living. Two studies have suggested that the debilitation and reduction in quality of life are severe, and that pain is a common problem.8,15 Pain Pain is the most frequent indication for surgery. Pain may be caused by compression off tendons, muscles, and nerves, bursitis or fracture of a pedunculated osteochondroma as the result of trauma. In some cases, no clear relationship is present between pain and the osteochondroma. In two major series, pain was experienced by 76% and 84%, of the studied patients, with a negative influence on the activities

Figure 1 Radiograph revealing a large osteochondroma of the humerus in a boy.

than 80%, it is diagnosed before the end of the first decade.6 Patients are now more aware of the inheritance of the disorder and consequently, the diagnosis is nowadays frequently made (or ruled out) in the first year of life. Osteochondromas are often first discovered on the ribs and the proximal tibia, where they can be clearly visible and palpable. Selected radiographs and genetic consultation can confirm the diagnosis MHE. In previous studies, there seemed to be a higher prevalence of MHE in males.5 More recent studies have found no evidence of sexual predominance.6,7,12 This earlier observation could have been attributable to a higher frequency of complications and a more pronounced clinical manifestation of the disease in males. The latter is in agreement with the results as reported by Pedrini et al., who found a significant correlation between male sex and more severe clinical presentations, especially for patients over 18 years old.9 Milder disease in females could be the result of hormonal factors, and earlier completion of puberty and growth arrest.

Problems and deformities most often encountered in patients with MHE Pain Psychosocial problems Functional impairment Cosmesis Restricted joint motion Long bone deformity Growth discrepancy between bones Growth disturbances Limb length discrepancy Short stature Brachydactyly Joint subluxation Neurovascular compression Impingement on tendons and muscles Nail plate deformity Scapular winging Spinal cord compression Haemothorax Obstetric problems Malignant degeneration

Imaging Conventional radiographs in MHE focus on the locations of osteochondromas in the axial and peripheral skeleton and reveal the most important deformities. Depending on age and indication, computerized tomography can be considered for regions that are difficult to visualize, such as the thorax, spine, and pelvis. Magnetic resonance Imaging is often used for preoperative evaluation. This modality provides more insight into the extent of the osteochondromas and the relation of the tumour to important

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Table 1

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of daily living, mood, and sleep.8,15 Pain on a daily basis was reported by 31% and 45.3%.and experienced more in adults in the series of Goud et al. (83% versus 63% in children). Together with the finding that two-thirds of adults reported having had surgery after the age of 18 years, these observations establish that problems associated with MHE persist into adulthood and continue after the growth of osteochondromas has ceased.

of the forearm are reported in 40e74% of the patients and can be unilateral or bilateral where one forearm is usually more severely involved than the other.5 The deformities produced by the forearm and wrist osteochondromas often impair function. During childhood, progressive limitation of forearm rotation frequently occurs. Forearm deformity was classified by Masada et al. into three groups based on morphological aspects.17 Group 1 comprises the most common deformity (55e61% of cases) characterized by ulnar shortening and radial bowing. (Figure 2) Most of the osteochondromas are located at the distal ulna. In Group 2 (22e33%), the radial head is dislocated with ulnar shortening and, often less pronounced radial bowing. (Figure 3) Dislocation is due to an osteochondroma on the proximal radial metaphysis in Group 2A, or on the distal ulna in Group 2B. Dislocation of the radial head in general leads to rotational impairment, particularly pronation. In Group 3 deformity, the primary

Activities of daily living In the Dutch population, MHE has a severe impact on daily life.8 Half of the patients with paid employment had experienced problems during their occupation, whereas 28% had to stop their activities and 21% needed adjustment to the workplace. Problems most often encountered were pain and loss of function. The choice of occupation seemed to be guided by problems associated with MHE, as most individuals did not perform heavy manual labour. The most common occupations reported were office duties or clerical work, occupations in the field of education, and management and information and communication technology. Of the children in school, more than half encountered serious problems, especially with physical education, writing, and computer-related tasks. Only a limited number of children received specific equipment or adapted school programmes to diminish their problems. The children were often bullied because of their disorder. Patients with MHE were substantially incapacitated in their ability to perform sports. The capacity of younger patients to participate in sports decreased significantly because of pain or functional limitations as they grew older. In adults, 50% of individuals who were previously active in sports had quit because of problems related to MHE. Most notable, team sports were often stopped.

Cosmesis Although there is little in the literature, in practice, cosmesis plays an important role. Large osteochondromas, axial deviation of bones and joints, upper and lower limb-length discrepancies, and short fingers and toes are often seen and are considered disfiguring. Furthermore, patients with MHE are often of short stature, with most studies reporting heights that were 0.5e1.0 standard deviation below the mean.5,7,8 According to Hosalkar et al., MHE is a significant risk factor for the development of abnormal scarring with keloid formation after surgical excision of osteochondromas. Informed consent preoperatively and prevention of abnormal scarring is therefore of importance.16 Growth disturbances Common growth disturbances in MHE are located in the forearm, hip, knee, and ankle and will be discussed in more detail. Periodic observation of children is of utmost importance to screen for the development of deformity and angular deviation of the long bones, as well-timed surgical treatment may be possible in selected cases to prevent progression or correct deformity. Forearm Osteochondromas are found in the distal forearm in up to 80% of patients and less frequently in the proximal forearm. Deformities

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Figure 2 Masada type 1 deformity of the forearm. The bowing of the radius, relative shortening of the ulna and osteochondroma on the distal ulna are clearly visualized.

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of the growth plate play a role. It has been suggested that the severity of the forearm deformity correlates strongly with the total body severity of MHE and the risk of malignant degeneration.18 There is an ongoing debate concerning the necessity for and the effect of surgical treatment in the early phase. Many adult patients with forearm osteochondromas, growth discrepancies and forearm deformity are functioning well without having had surgical treatment.19 Knowledge of the natural history of the disease and well-timed interventions are therefore essential when surgery is being considered to prevent, minimise or correct deformities, to resolve complaints and to provide a base for a minimal long-term restriction in the activities of daily living. The specific indications for surgery may be pain due to impingement of an osteochondroma, restriction of motion, functional deficits, loss of strength, marked deformity, and (an imminent) dislocation of the radial head. It is important to note that the shorter the ulna relative to the radius, the more loss of motion and function occurs. Several types of surgical procedures are possible, varying from excision of symptomatic osteochondromas to reconstruction of forearm deformities. In many cases, excision of osteochondromas associated with pain and/or limitation of motion is sufficient. Relief of pain can be expected (in selected cases) in 90% of patients. Early removal of osteochondromas during childhood can possibly delay or prevent progression of forearm deformities, but does not usually give full correction.20,21 Radial corrective osteotomy might be of benefit in patients with an increased ulnar deviation deformity of the wrist. The combination of radial osteotomy, ulnar lengthening, and excision of distal ulnar osteochondromas can be indicated in symptomatic malalignment when rebalancing of the forearm is necessary and the distal radioulnar joint can be reduced to a stable, more or less congruent joint after lengthening.17,22,23 Ulnar lengthening can be performed in a single-stage procedure or by gradual distraction with an external fixator. The rebalancing procedure can be beneficial for regaining more strength, and a better functional outcome, for cosmesis and also for stabilization of the radial head. One must be aware that reconstructive procedures performed at an early age often require reoperation because of recurrence of the deformity during growth.21,23 Early surgical intervention in Masada type 2 deformities was advised in the past.17 The maintenance of a reduced radial head following either ulnar lengthening or corrective osteotomy of the proximal ulna and radius, is uncertain. Creating a one-bone forearm was advocated as a salvage procedure for recalcitrant forearm deformities including a persistent and painful radial head dislocation.23 The major problems in predicting functional outcome following surgery in forearm MHE are the lack of long-term results of the various procedures in prospective studies and the lack of evidence concerning the question as to which procedure gives the optimal result in individual cases. Hand involvement is common in MHE with often more than 10 lesions in metacarpals, and proximal and middle phalanges. Brachydactyly is often present in one or two rays and generally is caused by metacarpal shortening. Angular deformity of the finger joints is less often seen.

Figure 3 Example of Masada type 2 deformity of the forearm with radial head dislocation.

osteochondromas are located in the distal radial metaphysis, with relative shortening of the radius (Figure 4). Several theories have been described about the aetiology of the deformities, in which the osteochondromas and/or disorders

Figure 4 Masada type 3 deformity with relative shortening of the radius.

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Knee and ankle Unilateral or bilateral valgus angulation is the most typical axial deformity in both the knee and ankle joint, occurring in approximately 50% of the individuals. In the knee, valgus angulation is most often found in the proximal tibial metaphysis, although angulation of the femur might also be present.24 (Figure 5) This could even lead to an oblique joint line orientation. Theoretically, valgus position of the joint and obliquity of the joint line may predispose to the development of degenerative joint disease at relatively early age.

Furthermore, progression of valgus deformity during growth might lead to lateral patella subluxation and patellofemoral complaints. Progression of angulation is often seen during rapid growth phase with acute increase in the size of the osteochondromas with simultaneously relative shortening of the fibula compared to the tibia. In the ankle joint, usually the growth disorder is complex with relative shortening of the fibula, an oblique course of the distal tibial epiphysis (growth disturbance), and medial subluxation of the talus.25 (Figure 6) Of concern is a high incidence of degenerative joint disease reported in the ankle joints of adult patients not treated before with greater tibiotalar tilt or ankle valgus.26 During growth, with excessive valgus angulation of the knee and ankle, temporary hemiepiphysiodesis can be performed for correction of the deformity.27 Hemiepiphysiodesis is a relatively minor surgical procedure that has been shown to provide gradual correction of the deformity. Periodic control, therefore, is essential in children to recognize mechanical axial distortion in the lower extremity at an early phase in order to make this procedure useful. In the skeletally mature patient corrective osteotomy might be indicated. In more severe ankle deformity, the relative shortening of the distal fibula cannot be corrected by hemiepiphysiodesis alone, and fibular lengthening might be considered.25 Hip Morphological change of the proximal femur is a common finding in MHE, with an increase in the diameter of the femoral neck due to osteochondroma formation and a high incidence of coxa valga. (Figure 7) Furthermore, acetabular dysplasia of the

Figure 6 Complex ankle growth disturbances with relative shortening of the fibula, an oblique alignment of the distal tibial epiphysis, and medial subluxation of the talus.

Figure 5 Valgus deformity of the knee. Notice the valgus deformity of the proximal tibia.

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Figure 7 Coxa valga of the left hip with osteochondroma on the medial side of the proximal femur.

Figure 8 MRI revealing pseudoaneurysm formation of the posterior tibial artery in the popliteal fossa as a consequence of a small osteochondroma (not shown) in an 8-years-old boy.

hip is found in a considerable number of patients. This dysplasia seems to develop during growth and could be caused by osteochondromas on the medial side of the femoral neck or in the periacetabular region leading to femoral lateralization. The aberrant morphology of the proximal femur may also play an important role.28 Coxa valga may be treated by early varus osteotomy. Acetabular dysplasia may require pelvic osteotomy to optimize coverage of the femoral head.

the growing years because of the potential risk of neurological lesions. Restricted joint motion Restricted and frequently painful motion of the joints is often encountered in MHE. In the upper extremity, forearm rotation may be limited because of osteochondromas extending into the interosseous interval between radius and ulna, thus obstructing full rotation. Excision of these osteochondromas, in particular during childhood might improve rotational capacity of the forearm. It is unsure if this prevents progression of deformity or even resolves or leads to full recovery of existent deformities.20,21

Other disorders Neurovascular disorders Impingement, entrapment or injury of neurovascular structures due to osteochondroma is often seen, particularly in the axillary region, the popliteal area, the proximal fibular region, and in the spinal canal. In the axillary region, osteochondromas on the medial side of the proximal humerus can be painful because of compression on the neurovascular structures. Excision of these lesions can relieve the symptoms, but is not without risk. Vascular problems are most often encountered in the lower extremities, with a reported prevalence as high as 11.3%, and the popliteal artery is most often involved.7 Vascular compression due to a growing osteochondroma can lead to pseudoaneurysm formation. (Figure 8) Other vascular problems that can occur are, among others, thrombosis, claudication, and ischaemia. In the proximal fibula, osteochondromas can become very large, and cause pain, functional impairment, and neurovascular compression because of their extent. (Figure 9) Neuropathy of the peroneal nerve can be the consequence of these osteochondromas (Figure 9), but structures in the popliteal fossa can also be involved. Resection of the proximal fibula including the osteochondromas might be indicated to remove all symptomatic lesions. In our experience, instability after this procedure is not a problem. In the vertebral column, osteochondromas can occur in up to 68% of the patients.29,30 Although most are located in the posterior part of the vertebra, MRI reveals the extension of the osteochondromas into the spinal canal in 27% of patients in the series reported by Roach et al.30 Although symptomatic compression of the medulla was relatively rare, the authors advised screening of all patients using MRI at least once during

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Figure 9 Large osteochondromas on the proximal fibula with considerable extension.

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aspect of the tibia.25 Ankle pain, a palpable mass and, when left untreated, plastic deformation of the eroded bone can be the reason for surgical intervention. Pain relief and prevention of progressive ankle deformity as well as remodelling of the distorted bone has been reported.25 In most cases, an anterolateral approach to the distal lower leg is indicated to remove all osteochondromas, obviously with preservation of the growth plate in children.

Function of the hip joint can be impaired due to osteochondromas on the proximal femur. Painful osteochondromas on the femoral neck that impair hip range of motion can, in selected cases, be treated by excision. In order to achieve this, surgical dislocation of the femoral head might be necessary to remove all symptomatic osteochondromas. The surgical technique, as reported above, is important in order to minimize the risk of developing of avascular necrosis of the femoral head.31 In the knee, maximum flexion may be limited due to osteochondromas in the popliteal region.

Pregnancy and birth Complications can occur during delivery due to the aberrant morphology of the pelvis or the presence of osteochondromas on the interior pelvis. In a Dutch study, more than half of the female participants who had one or more children reported complications during pregnancy and/or delivery.8 Cesarean section was necessary in 34% of these women, which was 2.5 times higher than that in the general Dutch population. Wicklund et al. reported similar results. In their series, two-thirds of women with MHE reported delivery by cesarean section, with 29% of these procedures being secondary to pelvic osteochondromas.7 According to the authors, women with MHE were at least twice as likely as the general population to have a cesarean section.

Scapular winging Osteochondromas are often located at the anterior part of the scapula and, when large enough, may present as scapular winging.32 (Figure 10) During abduction of the shoulder this can give rise to crepitus when the osteochondroma moves over the underlying ribs. Symptomatic, painful osteochondromas in this situation, require excision and this usually has a good result. CT or MRI is often necessary to reveal the extent and exact location of the osteochondroma(s) or when malignant transformation is suspected. Ribs Osteochondromas are frequently encountered on the ribs. In many cases they are located on the medial side of the ribs. The real prevalence of rib osteochondromas, therefore, is unknown. Excision of osteochondromas with or without partial resection of the underlying rib may be necessary due to pain or mechanical problems. Preoperative CT scanning is helpful to assess the location, extent and tumour aspects in more detail. Spontaneous haemothorax as a result of growing osteochondroma occurs sporadically.

Malignant degeneration The most feared complication of MHE is malignant transformation of an osteochondroma into a chondrosarcoma. The incidence of malignant transformation varies considerably in the literature, with an incidence of up to 25% reported in the older series. In more recent series this has been reduced to 3e6%.6e9 Malignant transformation is most frequently found in the pelvis, scapula and proximal part of the femur.5,12,33 Many of the chondrosarcomas are low-grade malignancies, and can be treated successfully with wide surgical excision. However, the pelvic region is a difficult location because chondrosarcomas can be very large by the time they present and involvement of neurovascular and visceral structures in the vicinity can make it difficult or even impossible to remove the tumour en bloc.34 There is no evidence that chondrosarcomas occur more frequently in families with an excessive form of MHE, in patients with either EXT1 or EXT2 mutations, or when patients have more osteochondromas.9,12 Malignant transformation in MHE seems to be diagnosed at a younger age than chondrosarcomas in nonMHE patients, most often in the first half of the fourth decade.8,35 Secondary peripheral chondrosarcoma is extremely rare before puberty and seldom occurs after the fifth decade of life. Painful enlargement of an osteochondroma after cessation of a patient’s growth is always suspicious for malignant degeneration. Because of the risk of malignant transformation, periodic surveillance is recommended. In adult patients with MHE, for instance, this should be done every 12e24 months depending on the locations at risk in order to detect early malignancies and provide adequate treatment.

Erosion of bone In the forearm and lower leg, growth of an osteochondroma can give rise to erosion and deformity of the adjacent bone. In the forearm this might lead to limited rotation and pain. In the lower leg, erosion of the distal fibula is most often seen and caused by an osteochondroma arising from the lateral side of the distal

Conclusion MHE is a chronic disease that leads to symptoms, impairment of function, disability, and physical disorders. MHE hampers social

Figure 10 Large osteochondroma on the ventral side of the scapula causing scapular winging and crepitus.

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16 Hosalkar H, Greenberg J, Gaugler RL, Dormans JP. Abnormal scarring with keloid formation after osteochondroma excision in children with multiple hereditary exostoses. J Pediatr Orthop 2007; 27: 333e7. 17 Masada K, Tsuyuguchi Y, Kawai H, Kawabata H, Noguchi K, Ono K. Operations for forearm deformity caused by multiple osteochondromas. J Bone Joint Surg Br 1989; 71B: 24e9. 18 Taniguchi K. A practical classification system for multiple cartilaginous exostosis in children. J Pediatr Orthop 1995; 15: 585e91. 19 Noonan KJ, Levenda A, Snead J, Feinberg JR, Mih A. Evaluation of the forearm in untreated adult subjects with multiple hereditary osteochondromatosis. J Bone Joint Surg Am 2002; 84A: 397e403. 20 Ishikawa J-I, Kato H, Fujioka F, Iwasaki N, Suenaga N, Minami A. Tumor location affects the results of simple excision for multiple osteochondromas in the forearm. J Bone Joint Surg Am 2007; 89A: 1238e47. 21 Akita S, Murase T, Yonenobu K, Shimada K, Masada K, Yoshikawa H. Long-term results of surgery for forearm deformities in patients with multiple cartilaginous exostoses. J Bone Joint Surg Am 2007; 89A: 1993e9. 22 Mader K, Gausepohl T, Pennig D. Shortening and deformity of radius and ulna in children: correction of axis and length by callus distraction. J Pediatr Orthop 2003; 12B: 183e91. 23 Waters PM, Bae DS. Osteochondromas. In: Waters PM, Bae DS, eds. Pediatric hand and upper limb surgery. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2012; 595e607. 24 Nawata K, Teshima R, Minamizaki T, Yamamoto K. Knee deformities in multiple hereditary exostoses: a longitudinal radiographic study. Clin Orthop 1995; 313: 194e9. 25 Chin KR, Kharazzi FD, Miller BS, Mankin HJ, Gebhardt MC. Osteochondromas of the distal aspect of the tibia or fibula. J Bone Joint Surg Am 2000; 82A: 1269e78. 26 Noonan KJ, Feinberg JR, Levenda A, Snead J, Wurtz LD. Natural history of multiple hereditary osteochondromatosis of the lower extremity and ankle. J Pediatr Orthop 2002; 22: 120e4. €cker R. Temporary screw epi27 Rupprecht M, Spiro AS, Rueger JM, Stu physiodesis of the distal tibia: a therapeutic option for ankle valgus in patients with hereditary multiple exostosis. J Pediatr Orthop 2011; 31: 89e94. 28 Porter DE, Benson MK, Hosney GA. The hip in hereditary multiple exostoses. J Bone Joint Surg Br 2001; 83B: 988e95. 29 Bess RS, Robbin MR, Bohlman HH, Thompson GH. Spinal exostoses. Spine 2005; 30: 774e80. 30 Roach JW, Klatt JWB, Faulkner ND. Involvement of the spine in patients with multiple hereditary exostoses. J Bone Joint Surg Am 2009; 91: 1942e8. 31 Siebenrock K-A, Ganz R. Osteochondroma of the femoral neck. Clin Orthop 2002; 394: 211e8. 32 Lazar MA, Kwon YW, Rokito AS. Snapping scapula syndrome. J Bone Joint Surg Am 2009; 91A: 2251e62. 33 Ahmed AR, Tan T-S, Unni KK, et al. Secondary chondrosarcoma in osteochondroma: report of 107 cases. Clin Orthop 2003; 411: 193e206. 34 Ham SJ, Heeg M, Horn JR van. Three patients with hereditary multiple exostoses and malignant degeneration of an osteochondroma located in the pelvis. Ned Tijdschr Geneeskd 2004; 148: 1732e8. 35 Ochsner PE. Multiple cartilaginous exostoses and neoplastic degeneration: review of the literature. Z Orthop Ihre Grenzgeb 1978; 116: 369e79.

functioning and has a profound effect on the activities of daily living, as well as paid work and school achievements. Pain can be a considerable problem. In children, periodic screening every six to twelve months is of importance because several growth disturbances can be treated by relatively simple procedures like hemiepiphysiodesis. In adults, regular clinical examination is recommended for early detection and adequate treatment of malignant transformation of osteochondroma into chondrosarcoma. A

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