Hereditary Multiple Osteochondromas

Clinical characteristics: Hereditary multiple osteochondromas (HMO), previously called hereditary multiple exostoses (HME), is characterized by growths of multiple osteochondromas, benign cartilage-capped bone tumors that grow outward from the metaphyses of long bones. Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and compression of peripheral nerves. The median age of diagnosis is three years; nearly all affected individuals are diagnosed by age 12 years. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk for malignant degeneration is low (~2%-5%).

Diagnosis/testing: The diagnosis of HMO is established in a proband with characteristic radiographic findings of multiple osteochondromas and/or a heterozygous pathogenic variant in EXT1 or EXT2 identified on molecular genetic testing.

Management: Treatment of manifestations: Painful lesions in the absence of bone deformity are treated with surgical excision that includes the cartilage cap and overlying perichondrium to prevent recurrence; forearm deformity is treated with excision of the osteochondromas, corrective osteotomies, and ulnar-lengthening procedures; though uncomplicated resection of osteochondromas in growing children is frequently reported, there is a theoretic risk of growth abnormality resulting from resection of periphyseal osteochondromas; angular misalignment of the lower limbs may be treated with hemiepiphysiodeses (or osteotomies) at the distal femur, proximal tibia, or distal tibia; leg-length inequalities greater than 2.5 cm are often treated with epiphysiodesis (growth plate arrest) of the longer leg or lengthening of the involved leg; early treatment of ankle deformity may prevent or decrease later deterioration of function; sarcomatous degeneration is treated by surgical resection.

Surveillance: Monitoring of the size of exostoses in adults may aid in early identification of malignant degeneration, but no cost/benefit analyses are available to support routine surveillance; a single screening MRI of the spine in children with HMO has been recommended by some to identify spinal lesions that may cause pressure on the spinal cord and would warrant close clinical follow up with excision of lesions that cause spinal cord impingement and/or symptoms. To date, there are no prospective studies to show a benefit of systematic screening MRI in asymptomatic individuals.

Genetic counseling: HMO is inherited in an autosomal dominant manner. Penetrance is approximately 96% in females and 100% in males. In 10% of affected individuals HMO is the result of a de novo pathogenic variant. Offspring of an affected individual are at a 50% risk of inheriting the pathogenic variant. Prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible if the pathogenic variant in a family is known.