Hereditary multiple exostoses

Last revised by Yaïr Glick on 1 Apr 2024

Hereditary multiple exostoses/osteochondromas, also known as diaphyseal aclasisosteochondromatosis, or simply multiple osteochondromas, is an autosomal dominant condition, characterized by the development of multiple osteochondromas.

Hereditary multiple exostoses demonstrate an autosomal dominant inheritance pattern, with incomplete penetrance in females, leading to a slight male predominance. Prevalence is estimated at 1 in 50,000 people 6. The number of exostoses, the degree, and type of angular deformity, and even the rate of malignant transformation, vary significantly, even within families.

In rare circumstances, hereditary multiple exostoses occurs together with enchondromatosis in a condition known as metachondromatosis.

Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition) 6:

  • essential: ≥2 radiological osteochondromas at the juxtaepiphyseal region of the long bones and positive family history and/or EXT gene germline mutation

Most patients are diagnosed by the age of 5 years and virtually all are diagnosed by the age of 12 years. Patients may be asymptomatic with a few small lesions or may be significantly deformed by multiple large osteochondromas. 

Hereditary multiple exostoses can involve any bone in the body except for the calvarium 5. Common sites of involvement include the distal femur, proximal tibia, wrist and hands, humerus, ankle, pelvis, and ribs.

Hereditary multiple exostoses is thought to result from EXT1EXT2, or EXT3 gene mutations on chromosomes 8q24 (EXT1), 11p11-13 (EXT2), and 19p (EXT34,5.

Apart from being multiple, imaging features are identical to solitary osteochondromas. The skeletal distribution of lesions can vary significantly, with some authors reporting typical distribution as bilateral and symmetric, whereas others report a strong unilateral predominance.

The condition is often associated with a broadened shaft at the end of long bones, hence the term 'diaphyseal aclasis'.

Complications are similar to those of solitary osteochondroma and include:

Malignant transformation is more common than in sporadic cases, with transformation rates reported as high as 25% (lower rates of 3-5% have also been published) 3. The mnemonic GLAD PaST 1 lists the associations with sarcomatous transformation.

Refer to the generic osteochondroma article for more information.

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