Multiple Cartilaginous Exostoses – Definition
Multiple cartilaginous exostosis syndrome (OMIM 133700, 133701, 600209) is a rare disease in which multiple cartilaginous exostoses or osteochondromas occur, mainly on the epiphyses of the long bones. There is a risk of malignant degeneration into chondrosarcoma.
Synonyms:
Hereditary multiple exostoses, multiple osteochondromatosis, osteochondromatosis
Genes:
EXT1 (8q24.11) or EXT2 (11p11.2)
Gene product:
Exostosin glycosyltransferase
Function:
Heparan sulfate biosynthesis
Pattern of inheritance:
Autosomal dominant, de novo
Prevalence:
up to 1:50.000
Genotype-phenotype correlation:
–
Penetrance:
96% for women and 100% for men
Multiple Cartilaginous Exostoses – Diagnosis
The diagnosis is made clinically and radiologically when two or more osteochondromas or cartilaginous exostoses occur, and another diagnosis seems unlikely. Genetic testing confirms the diagnosis. The age of diagnosis is often between 5 and 7 years.
Differential Diagnoses
- Ollier’s disease and Maffucci syndrome
- Langer-Giedion syndrome
- Potocki-Shaffer syndrome
- Gardner’s disease
- Menkes syndrome
- Fibrodysplasia Ossificans Progressiva
Clinical Presentation
Cartilaginous exostoses are benign bone tumors with a cartilaginous cap that develop in childhood from the growth plates and ossify with the completion of growth or closure of the growth plates. The number of exostoses per patient varies greatly, with an average of 15-18. They can occur on any bone that is formed by endochondral ossification. The knee is most commonly affected by the distal femur (70%), proximal tibia (71%), and proximal fibula (27%); the upper extremity is also regularly affected. Other localizations, such as hands, scapulae, ribs, spine, and pelvis, are also possible.
The most common symptoms are pain due to irritation or displacement of adjacent structures such as muscles, nerves, blood vessels, or tendons. This can result in restricted joint movement, impaired height growth, or the development of deformities in the affected bones. Differences in leg length are widespread and indicate a need for surgical intervention. Rare complications due to the unfavorable localization of the exostoses include pneumothoraces, haematothoraces, chest pain, neurological deficits, and dysphagia.
Malignant degeneration into chondrosarcoma occurs in 0.5-5% of patients, usually before age 40. The most common localizations are the pelvis, scapula, proximal femur, spine, or ribs. The risk of degeneration appears to be 1.5-2 times higher with EXT1 pathogenic variants compared to EXT2 pathogenic variants. Warning signs of malignant degeneration are pain and tumor growth after puberty.
Special Features of Treatment
Current treatment consists of the surgical removal of symptomatic exostoses and the correction of skeletal deformities. Surgical intervention is not indicated for asymptomatic exostoses. Drug therapy has not yet been approved.
Diagnosis of Multiple Cartilaginous Exostoses- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of Multiple Cartilaginous Exostoses - What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
Below you will find the recommendations from the AACR Guidelines 2024.
Chondrosarcomas
- Annual clinical examination from birth
- Whole-body MRI
- in early adolescence (approximately 12 years of age) can be considered as a baseline examination
- from 20-40 years, an annual whole-body MRI can be considered
- From diagnosis every 2-3 years, targeted MRI examinations for lesions in the pelvis or scapula should be considered, especially in male patients and patients with EXT1 variant
- In case of pain or rapidly increasing tumour size, a targeted MRI or CT of the lesion should be performed
- For cartilage caps <2cm, a biopsy should be considered
- Due to the high number of osteochondromas and the low tendency to transform into chondrosarcomas, regular imaging of all lesions is NOT recommended
