Ollier’s Disease and Maffucci Syndrome – Definition
Ollier disease (OD, OMIM #166000) and Maffucci syndrome (MS, OMIM #614569) are enchondromatoses associated with a pathogenic variant in the IDH1 or IDH 2 gene. The two diseases differ in the additional presence of multiple soft tissue hemangiomas or lymphangiomas in Maffucci syndrome. What they have in common is a tendency to malignant degeneration into chondrosarcomas. Affected patients also have an increased risk of developing other tumors, such as brain tumors or visceral tumors.
Synonyms:
Multiple Enchondromatosis, Hemienchondromatosis
Genes:
IDH1 and IDH2 gene
Gene product:
Isocitrate-dehydrogenase 1+2
Function:
Decrease in D-2-hydroxyglutarate (D-2-HG), an oncometabolite that accumulates in the cell when its breakdown is reduced and, together with other risk factors, can promote cancer development.
Pattern of inheritance:
Mosaicism in somatic mutation
Prevalence:
For M. Ollier 1:100,000, Maffucci syndrome <200 cases known worldwide (as of 09/22)
Genotype-phenotype correlation:
Unknown
Penetrance:
Unknown
Ollier’s Disease and Maffucci Syndrome – Diagnosis
The diagnosis is mainly made clinically and radiologically. Multiple (>3) asymmetrical enchondromas are found, predominantly localized in the epiphyseal region, followed by the metaphysis and diaphysis. A biopsy of the enchondromas can confirm the diagnosis.
Maffucci syndrome presents clinically like Ollier’s disease but is associated with soft tissue hemangiomas and lymphangiomas and can, therefore, be differentiated in the clinical diagnosis.
In addition, genetic diagnostics should be carried out for mutations in the IDH1 and IDH2 genes, as these are frequently associated with Ollier’s disease and Maffucci syndrome.
Differential Diagnoses
- Multiple cartilaginous exostosis
- Metachondromatosis
- Spondyloenchondroplasia with immune dysregulation
- Congenital spondyloepiphyseal dysplasia
Clinical Presentation
The clinical appearance is accompanied by typical symptoms of benign bone tumors, such as localized pain, swelling, malformations, and even spontaneous bone fractures.
Depending on the location, longitudinal growth may also be restricted. This can result in scoliosis, leg length discrepancy, or other skeletal malformations.
Enchondromas tend to malignantly degenerate into chondrosarcoma (approximately 1/3), although this often only occurs after the skeleton fully matures. Enchondromas of the long tubular bones, especially of the lower extremities, tend to degenerate sooner than smaller bones (hand or foot). In general, single enchondromas tend to degenerate lower than multiple enchondromas in Ollier’s disease or Maffucci syndrome.
Cancer Predisposition
- Chondrosarcomas
- Brain tumors (especially gliomas)
- Visceral tumors
- malignant vascular malformations (especially in Maffucci syndrome)
- juvenile granulosa cell tumors
- Ovarian carcinoma
Special Features of Treatment
The only treatment currently available is the surgical removal of symptomatic enchondromas, although these are often recurrent. Surgical intervention is not indicated for asymptomatic enchondromas. Drug therapy is not yet known.
Diagnosis of Ollier’s Disease and Maffucci Syndrome- 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 Ollier’s Disease and Maffucci Syndrome- 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
Due to the limited data available, there are currently no evidence-based guidelines for the early detection of cancer in OD or MS.
The following is currently recommended:
- Whole-body MRI at diagnosis to visualize all lesions and affected bone, as well as screening for the presence of vascular abnormalities
- Measurement of D-2-hydroxyglutaric acid in urine after diagnosis
- Genetic diagnostics for pathogenic variants in the IDH1 and IDH2 gene, as well as assessment of the DNA mosaic
- X-ray control of known lesions every 2-3 years, in the case of localizations such as pelvis or shoulder blade or a size over 5-6cm, an MRI can be considered as an alternative
- Thorough clinical examination and consultation every year, adjusted if necessary
- time interval depending on symptom burden
- From the age of 25, a whole-body MRI is also recommended for all patients (corresponds to the median age of onset of malignant disease in Ollier’s disease), which can be repeated annually depending on the findings
