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
Below you will find the recommendations from the AACR Guidelines 2024.
Chondrosarcomas
- Whole-body MRI for diagnosis and if an examination is possible without a general anaesthetic
- Whole-body MRI in childhood only once as a baseline examination, cranial MRI only in the case of neurological symptoms
- Whole-body MRI incl. cranial MRI every 1-2 years from 20 years of age
- Clinical check-ups from birth to the end of adolescence every 6-12 months, from adulthood every 12-24 months
- Regular x-rays of known lesions every 2-3 years
- Annual targeted MRI examination for lesions >5-6cm or for lesions in the pelvis or scapula should be considered
- In case of pain or increasing tumour size, a targeted MRI of the lesion and a biopsy should be performed
Vascular malignancies, gliomas, juvenile granulosa cell tumours
- Clinical check-ups including neurological examination from birth to the end of adolescence every 6-12 months, from adulthood every 12-24 months
- Pay particular attention to abdominal pain in women and, if necessary, arrange for additional diagnostics
