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 .
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   .