Ollier disease

Abstract

Enchondromas are common intraosseous, usually benign cartilaginous tumors, that develop in close proximity to growth plate cartilage. When multiple enchondromas are present, the condition is called enchondromatosis also known as Ollier disease (WHO terminology). The estimated prevalence of Ollier disease is 1/100,000. Clinical manifestations often appear in the first decade of life. Ollier disease is characterized by an asymmetric distribution of cartilage lesions and these can be extremely variable (in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, requirement for surgery). Clinical problems caused by enchondromas include skeletal deformities, limb-length discrepancy, and the potential risk for malignant change to chondrosarcoma. The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci syndrome. Until now both Ollier disease and Maffucci syndrome have only occurred in isolated patients and not familial. It remains uncertain whether the disorder is caused by a single gene defect or by combinations of (germ-line and/or somatic) mutations. The diagnosis is based on clinical and conventional radiological evaluations. Histological analysis has a limited role and is mainly used if malignancy is suspected. There is no medical treatment for enchondromatosis. Surgery is indicated in case of complications (pathological fractures, growth defect, malignant transformation). The prognosis for Ollier disease is difficult to assess. As is generally the case, forms with an early onset appear more severe. Enchondromas in Ollier disease present a risk of malignant transformation of enchondromas into chondrosarcomas.

Figure 1

Roentgenographs showing enchondromas localized in the upper part of the humerus (fig 1a and lower part of the radius (fig 1b) of a girl 7 years of age affected with Ollier disease. Courtesy of Dr Fitoussi, Hôpital Robert Debré, Paris, France.

Figure 2

Importance of IHH and PTHrP signaling in the modulation of chondrocyte proliferation and differentiation during endochondral bone formation. PTHrP is synthesized by chondrocytes and perichondrial cells in the periarticular growth plate. PTHrP diffuses toward the prehypertrohic zone where it binds to and activates its receptor, the PTHR1, and thereby maintains chondrocyte proliferation and delays chondrocyte differentiation into pre-hypertrophic and hypertrophic chondrocytes. After chondrocytes stop proliferating at the transition from a proliferating into a hypertrophic phenotype, they synthesize IHH. IHH acts to indirectly increase the synthesis of PTHrP. IHH and PTHrP thus participate in a negative feed-back loop that serves to regulate the rate and synchrony of growth plate chondrocytes. Besides increasing PTHrP synthesis, IHH also stimulates, both directly and indirectly, chondrocyte proliferation and inhibits their terminal differentiation. Parathyroid hormone-related protein (PTHrP) Indian Hedgehog (IHH) Parathyroid hormone receptor 1 (PTHR1)