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Hereditary multiple exostoses

Introduction

Hereditary multiple exostoses is one of the most common skeletal dysplasias seen by orthopaedic surgeons with an estimated prevalence of approximately 1 in 18,000. It is characterized by cartilage capped prominences that develop from the epiphyses of the long bones. The disorder is of autosomal dominant inheritance, with penetrance approaching 96%.

Numerous genetic studies have found anomalies on at least three different genes, termed exostosin (EXT) genes, making this a genetically heterogeneous disorder. The three described EXT loci have been recently mapped: EXT1 on chromosome 8, EXT2 on chromosome 11, and EXT3 on chromosome 19. According to linkage analysis, the EXT1 and EXT2 loci appear to be altered in the majority of families while, EXT3, which has not been fully isolated and characterized, is probably less frequently affected. EXT1 and EXT2 function as tumor-suppressor genes and encode two homologous glycoproteins which are expressed throughout the musculoskeletal system. Both glycoproteins are glycosyltransferases which are located in the membrane of the endoplasmic reticulum and have a role in modifying and enhancing the synthesis and expression of heparan sulfate. Heparan sulfate is a complex polysaccharide that has been implicated in a variety of cellular processes including cell adhesion, growth factor signaling, and cell proliferation. The gross pathologic and microscopic features of hereditary multiple exostoses are similar to those described for solitary osteochondromas.

Clinical Features

The exostoses usually appear after age 3 to 4 years. On presentation, 5 or 6 exostoses typically may be found, involving both the upper and lower limbs. Over time, the upper and lower extremities may appear short in relation to the trunk. Shortening of the limbs is usually disproportionate. Affected persons are at the low end of normal for stature. Distal femur, proximal tibia, proximal humerus, scapula and ribs, proximal fibula, and distal radius and ulna are the most commonly involved sites.

Problems from this condition may be divided into four categories: 1) local prominence and impingement by the exostoses; 2) asymmetric growth of two-bone segments, such as the forearm and the leg; 3) limb-length inequality; and 4) late degeneration into chondrosarcoma.

Local prominence may cause pressure on muscles, tendons, or nerves, resulting in pain, limited motion (i.e., forearm motion), or nerve palsy (i.e., peroneal palsy from a proximal fibular lesion). Asymmetric growth often results in angular deformities of the upper and lower limbs. Valgus may develop at the wrist, knee, and ankle. The natural history of these deformities has been described as progressive, with variable weakness, functional impairment, and worsening cosmetic deformity of the extremity. Limb-length inequality is common due to more involvement of one limb than the other. Malignant transformation in the pediatric age group is very rare, and is difficult to monitor. The most practical way is educating patients and parents about signs of malignant transformation, such as increased growth of an exostosis or pain over an exostosis.

Radiographic Findings

Unlike solitary osteochondromas, hereditary multiple exostoses involve a significantly greater portion of the metaphysis or diaphysis and are generally more irregular in shape. Over time, lesions that begin in the metaphyseal region migrate into the diaphysis of the long bones. The exostoses vary in number, size, and configuration. Like solitary osteochondromas, they may grow perpendicular to the bone in a sessile or pedunculated fashion.

They nearly always point away from the physis. The cortex of the exostosis is contiguous with that of the bone itself.  Exostoses on the undersurface of the scapula may be identified on plain films, but are best evaluated by CT.
The ulna is shorter than the radius and the radius is bowed laterally, with its concavity towards the short ulna. Often the distal end of the ulna is more severely affected than the distal end of the radius, leading to this discrepancy in length. Subluxation/dislocation of the radial head occurs and is usually associated with a negative ulnar variance. The femoral necks are usually wide and in valgus. Genu valgum and ankle valgus may be seen.

Orthopaedic Considerations

Because the lesions are numerous and multiple bones are affected, a careful evaluation of the upper and lower limbs, including range of motion of the joints, neurologic examination, and measurement of the angular deformities, should be performed. Any exostoses causing significant symptoms should be excised. Reasonable indications include pain, growth disturbance leading to angular deformity or limb-length discrepancy, joint motion compromised by juxta-articular lesions, soft tissue impingement or tethering, false aneurysm produced by an osteochondroma, painful bursa formation, obvious cosmetic deformity, and a rapid increase in the size of a lesion.

Osteochondromas involving the forearm frequently lead to surgical intervention. Early excision of the lesions on the radius and ulna does not alter or correct existing deformity, but it may delay progression of the deformity. If ulnar shortening has occurred with bowing of the radius, lengthening of the ulna combined with distal radial osteotomy or hemiepiphyseodesis has been found effective in correcting the deformity. Painful radial head dislocations can be safely excised following skeletal maturity. Significant valgus deformities of the knee and ankle are treated by osteotomy or hemiepiphyseodesis when young, or corrective varus osteotomy when older (near maturity). Epiphyseodesis is the most appropriate treatment for significant limb-length inequality in growing patients.

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