Review Article Enchondromatosis: insights on the different subtypes
Twinkal C. Pansuriya, Herman M. Kroon, Judith V.M.G. Bovee
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
Received May 31, 2010, accepted June 18, 2010, available online June 26, 2010
Abstract: Enchondromatosis is a rare, heterogeneous skeletal disorder in which patients have multiple enchondromas. Enchondromas are benign hyaline cartilage forming tumors in the medulla of metaphyseal bone. The disorder manifests itself early in childhood without any significant gender bias. Enchondromatosis encompasses several different subtypes of which Ollier disease and Maffucci syndrome are most common, while the other subtypes (metachondromatosis, genochondromatosis, spondyloenchondrodysplasia, dysspondyloenchondromatosis and cheirospondyloenchondromatosis) are extremely rare. Most subtypes are non-hereditary, while some are autosomal dominant or recessive. The gene(s) causing the different enchondromatosis syndromes are largely unknown. They should be distinguished and adequately diagnosed, not only to guide therapeutic decisions and genetic counseling, but also with respect to research into their etiology. For a long time enchondromas have been considered a developmental disorder caused by the failure of normal endochondral bone formation. With the identification of genetic abnormalities in enchondromas however, they were being thought of as neoplasms. Active hedgehog signaling is reported to be important for enchondroma development and PTH1R mutations have been identified in ~10% of Ollier patients. One can therefore speculate that the gene(s) causing the different enchondromatosis subtypes are involved in hedgehog/PTH1R growth plate signaling. Adequate distinction within future studies will shed light on whether these subtypes are different ends of a spectrum caused by a single gene, or that they represent truely different diseases. We therefore review the available clinical information for all enchondromatosis subtypes and discuss the little molecular data available hinting towards their cause. (IJCEP1005009).
Address all correspondence to: Judith V.M.G.Bovee, MD, PhD Department of Pathology Leiden University Medical Center Albinusdreef 2, 2333 ZA Leiden The Netherlands. Tel: +31715266617, Fax: +31715266952 Email: J.V.M.G.Bovee@lumc.nl