Ollier disease (ORPHA:296)
A rare primary bone dysplasia characterized by multiple enchondromas (benign cartilage-forming tumors). The lesions are generally unilateral or asymmetrically distributed. The most common affected site is the appendicular skeleton.
Epidemiology
Prevalence of Ollier disease (OD) is estimated at 1/100,000, but mild presentations without skeletal deformities may be underdiagnosed. OD is approximately evenly represented in both sexes.
Clinical description
Clinical expression of the disease is variable, it can involve a single bone segment or multiple limbs. The lesions develop during childhood and adolescence (median age of 13), but presentation in adulthood is also possible. It usually manifests with painless bony masses, which mostly occur in an asymmetric bilateral fashion, albeit symmetrical distribution has been described. The most frequently affected sites are the bones of the appendicular skeleton, in particular the hands (phalanges and metacarpals) and the metaphyses and diaphyses of the long tubular bones (i.e. femur, tibia, humerus). Rarely, spine, ribs, sternum, and skull can be involved. Pelvis involvement can lead to scoliosis. Patients present with multiple swelling, leading to apparent morphological abnormalities. Rarely, bone shortening can be the only presenting feature. Deformity around the joints, angular deformity, genu valgus, cubitus varus, joint mobility limitation, leg-length discrepancy, pathological fractures, facial asymmetry, and cranial nerve palsy can also be associated. OD is associated with an increased risk of malignancies compared to the general population such as chondrosarcoma (variably estimated but as high as 50% in some studies), central nervous system tumors, and occasionally gliomas, acute myeloid leukemia, and juvenile granulosa cell tumors.
Etiology
The disease is due to somatic variants in IDH1 (2q34), IDH2 (15q26.1) and, more rarely, PTH1R (3p21.31), coding for isocitrate dehydrogenase 1, 2 and parathyroid hormone 1 receptor, respectively. Mutations are limited to the involved tissues. No familial case has been reported.
Diagnostic methods
The diagnosis relies on clinical features and imaging findings, in particular conventional radiological evaluation. Enchondromas appear as slow growing, radiolucent defects that originate in the metaphyses. Both CT and MRI are useful for monitoring the disease, with MRI allowing evaluation of intraosseous and soft tissue involvement.
Differential diagnosis
The differential diagnoses include multiple hereditary exostosis (also known as multiple osteochondromas), osteitis fibrosa cystica, chondroma and chondrosarcoma.
Management and treatment
No specific therapy exists for OD. The management is usually conservative, but surgical approach can be proposed and is at present the only option when complications (e.g. pathological fractures) occur. Because of the risk of malignant transformation, annual monitoring of patients is recommended. Scintigraphy, ultrasound or biopsy for histological examination can be indicated for surveillance of lesions that become symptomatic (pain, increase in size) or suspected of malignant transformation. No specific guideline is available for the surveillance of other cancers risk due to the small number of patients reported and the limited data about the real incidence of other neoplasms in OD.
Prognosis
Prognosis is difficult to assess due to the wide clinical expression and variability of the disease. Depending on the extent of skeletal involvement, OD may result in severe deformities with functional and quality of life repercussions. Negative predictors are early onset, gross asymmetrical distribution, with severe shortening or deformity of the skeletal segment involved (e.g. limb asymmetry or phalangeal deformity) and malignant transformation (which is the most serious complication, potentially affecting the life span).

                            Last update: 
                            May 2023


                            - Expert reviewer(s): 
                            Dr Luca SANGIORGI | ERN BOND*


                                * European Reference Network