Multiple Hereditary Exostosis

Multiple Hereditary Exostosis (HME)

OBJECTIVES:

Describe the anatomic features of HME
Discuss the genetics of HME
Discuss the natural history of HME
Identify surgical indications for HME
Discuss proper monitoring for patients with HME
Identify the known risk of malignancy in patients with HME

HEREDITARY MULTIPLE EXOSTOSIS

MULTIPLE CARTILAGINOUS EXOSTOSES

DIAPHYSEAL ACLASIS

MULTIPLE OSTEOCHONDROMATOSIS

Multiple Hereditary Exostosis (HME or EXT) is an autosomal dominant trait characterized by multiple exostosis or cartilage capped bony prominences typically arising in the metaphyseal region of long bones, although the diaphysis, spine, and ribs may also be involved. It is commonly seen by orthopedists, perhaps because the lesions are often quite noticeable.

The osteochondromas are typically asymptomatic. The primary difficulties arise either from their mass effect, physeal growth disturbance, fracture within the osseous portion or from potential malignant degeneration. Mass effects have been described resulting in spinal cord or tracheal compression from vertebral loci, peripheral nerve compression in the extremities, joint subluxation and dislocation, vascular disruption and visceral compression of nearly every location in the body. Growth abnormalities are typically most significant in the two bone segments, the forearm and the leg, but can also result in deformities about any effected physis. Clinically, the exostoses occur in multiple metaphyseal areas. The patients are often shorter than normal by ½ to 1 standard deviation. In growing children, the lesions can cause growth disturbances, limb shortening, and significant deformities, particularly in the two bone segments of the forearm and leg. They can also cause impingement upon the joints and soft tissues including muscles and nerves. There is also a high incidence of generalized pain which is often unrecognized.

Genetics: There are three know chromosomal loci for the disorder, EXT1 (chromosome 8q24), EXT2 (chromosome 11), EXT3 (chromosome 19) with some evidence for an additional locus. Multiple osteochondromas also occur in metachondromatosis and Langer-Giedion syndrome also known as trichorhinophalangeal syndrome type II. The exostosis from metachondromatosis and dysplasia epiphysealis hemimelica do not come from the EXT genes. Malignancy is thought to arise because the encoding genes are classic tumor suppressors. HME results in an autosomal dominant pattern when one of the genes is effected. Disruption of the other gene then allows malignant transformation. Recently, however, there is some evidence that EXT1 and EXT2 encode endoplasmic reticulum–resident type II transmembrane glycoproteins which are involved in the regulation of cell-surface heparin sulfate proteoglycans (HSPGs) that, in turn, are integral to the diffusion of several families of cell-signaling molecules. Clinically, patients with EXT 1 typically have more involvement than those with other types.

Risk of Malignancy: The overall risk of malignant degeneration widely varied in the literature. Probably the best estimate is 0.57% but is very difficult to obtain an accurate estimate since it is those who develop malignancy who come to medical attention. The mean age of malignant degeneration is 31 and rarely occurs before age 10 or after age 50. Particular areas of concern are the pelvis, proximal femur, shoulder girdle and the ribs. Patients should be aware of the malignant potential and report any increased pain or size of lesions. PET scanning shows some promise in distinguishing benign from malignant lesions.

Generally, surgery is recommended for nerve or vessel compression or concern about malignancy. It is also quite effective to correct deformity but is more controversial in whether surgery can improve function or prevent future problems.

Specific locations:

Spine – Solitary osteotchondromas are a more frequent cause of spinal problems than HME. They more commonly present with posterior cervical spine osteochondromas than lesions elsewhere.

Upper Extremity – the forearm is often significantly effected with a deformity similar to Madelungs. Burgess and Cates reviewed a large series of patients with radial bowing and found no association with ulnar variance indicating that the deformity is not from an ulnar tether although an ulnar tether may have a significant role in radial head dislocation. Surgically, correction of deformity is not necessarily correlated with improved function. A modified Suave-Kapankdi procedure can provide improved stability and still allow supination and pronation though hemiepiphyseal stapling appears to be a simpler and reliable procedure.

Lower Extremity- The distal femur and proximal tibia are commonly affected and can develop significant deformity, typically valgus. Although osteotomies may be required, hemiepiphyseodesis is often much simpler and effective. Ankle function appears to decrease with significant ankle valgus, and the ankle valgus can often be successfully treated with hemiepiphyseodesis.

Key Points:

HME comes in several variants
Lesions are associated with deformities and dislocations of the bones and joints
There is a small, but real malignant potential with MHE.
The osteochondromas can cause significant mass effect on nerves, vessels, and other organs.

Reference List

Beals RK. The treatment of ankle valgus by surface epiphysiodesis. Clin Orthop Relat Res 1991 May;(266):162-9.
Cheung PK, McCormick C, Crawford BE, Esko JD, Tufaro F, Duncan G. Etiological point mutations in the hereditary multiple exostoses gene EXT1: a functional analysis of heparan sulfate polymerase activity. Am J Hum Genet 2001 Jul;69(1):55-66.
Danielsson LG, el-Haddad I. Winged scapula due to osteochondroma. Report of 3 children. Acta Orthop Scand 1989 Dec;60(6):728-9.
Hecht JT, Hogue D, Wang Y, Blanton SH, Wagner M, Strong LC, et al. Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases and EXT-associated malignancies. Am J Hum Genet 1997 Jan;60(1):80-6.
Johnston CE, Sklar F. Multiple hereditary exostoses with spinal cord compression. Orthopedics 1988 Aug;11(8):1213-6.
Matsubara H, Tsuchiya H, Sakurakichi K, Yamashiro T, Watanabe K, Tomita K. Correction and lengthening for deformities of the forearm in multiple cartilaginous exostoses. J Orthop Sci 2006 Oct;11(5):459-66.
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 Jan;22(1):120-4.
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 Mar;84-A(3):397-403.
Peterson HA. Multiple hereditary osteochondromata. Clin Orthop Relat Res 1989 Feb;(239):222-30.
Shin EK, Jones NF, Lawrence JF. Treatment of multiple hereditary osteochondromas of the forearm in children: a study of surgical procedures. J Bone Joint Surg Br 2006 Feb;88(2):255-60.
Stieber JR, Dormans JP. Manifestations of hereditary multiple exostoses. J Am Acad Orthop Surg 2005 Mar;13(2):110-20.
Theodorou SD, Karamitsos S, Tsouparopoulos D, Hatzipavlou AG. Rare complications of exostosis. Fractures and injury to the common peroneal nerve. Acta Orthop Belg 1978 Jul;44(4):496-505.
Vasseur MA, Fabre O. Vascular complications of osteochondromas. J Vasc Surg 2000 Mar;31(3):532-8.