Clinical Guidance

No clinically relevant genotype-phenotype correlations for EXT1 or EXT2 have been identified.

Source: GeneReviews — "Hereditary Multiple Osteochondromas"

Penetrance

The penetrance is estimated to be 96% in females and 100% in males . Most published instances of reduced penetrance have occurred in females. However, comprehensive skeletal radiographs have not been performed in most of these instances.

Source: GeneReviews — "Hereditary Multiple Osteochondromas"

Diagnostic Criteria

No consensus clinical diagnostic criteria for hereditary multiple osteochondromas (HMO) have been published.

Suggestive Findings

HMO should be suspected in individuals with the following radiographic features and/or family history.

Source: GeneReviews — "Hereditary Multiple Osteochondromas"

Differential Diagnosis

Solitary osteochrondroma. Skeletal surveys suggest that a solitary osteochondroma, a common benign bone tumor, can be found in 1%-2% of the population . Solitary osteochondromas demonstrate growth patterns similar to those of multiple osteochondromas. Conditions that may be confused with a solitary osteochondroma include juxtacortical osteosarcoma, extraskeletal osteosarcoma, and heterotopic ossification. Plain radiographs or CT are often helpful in distinguishing these lesions from osteochondromas. Typically, none of these conditions display the continuity of cancellous and cortical bone from the host bone to the lesion characteristic of hereditary multiple osteochondromas (HMO). Genetic conditions in which multiple osteochondromas occur are summarized in . Table 3. Hereditary Multiple Osteochondromas: Differential Diagnosis

Management Guidelines

No clinical practice guidelines for hereditary multiple osteochondromas (HMO) (also known as multiple hereditary exostoses [MHE]) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with HMO, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Hereditary Multiple Osteochondromas: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "Hereditary Multiple Osteochondromas"

Therapies Under Investigation

A clinical trial of the retinoic acid receptor gamma agonist palovarotene for individuals younger than age 14 years with HMO was terminated secondary to concerns for early growth plate closure in a study utilizing the same drug for fibrodysplasia dissecans progressiva. Roneparstat, a potent low-molecular-weight heparin derivative and inhibitor of enzyme heparinase, has also been investigated, as preclinical studies have shown that the drug can inhibit chondrogenesis, which is the initial step of osteochondroma development. However, no clinical studies have occurred. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Hereditary Multiple Osteochondromas"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. Hereditary Multiple Osteochondromas: Recommended Surveillance

Source: GeneReviews — "Hereditary Multiple Osteochondromas"