Ollier disease

Ollier disease is a disorder characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures.

The signs and symptoms of Ollier disease may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Ollier disease, people with this disorder generally have short stature and underdeveloped muscles.

Although the enchondromas associated with Ollier disease start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Ollier disease also have an increased risk of other cancers, such as ovarian cancer or liver cancer.

People with Ollier disease usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities.

A related disorder called Maffucci syndrome also involves multiple enchondromas but is distinguished by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas).

Ollier disease is estimated to occur in 1 in 100,000 people.

In most people with Ollier disease, the disorder is caused by mutations in the IDH1 or IDH2 gene. These genes provide instructions for making enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. IDH1 or IDH2 gene mutations cause the enzyme produced from the respective gene to take on a new, abnormal function. Although these mutations have been found in some cells of enchondromas in people with Ollier disease, the relationship between the mutations and the signs and symptoms of the disorder is not well understood.

Mutations in other genes may also account for some cases of Ollier disease.

Genetic Testing Information

• Genetic Testing Registry: Enchondromatosis

Genetic and Rare Diseases Information Center

• Ollier disease

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• ENCHONDROMATOSIS, MULTIPLE, OLLIER TYPE

Scientific Articles on PubMed

• PubMed

• Amary MF, Damato S, Halai D, Eskandarpour M, Berisha F, Bonar F, McCarthy S, Fantin VR, Straley KS, Lobo S, Aston W, Green CL, Gale RE, Tirabosco R, Futreal A, Campbell P, Presneau N, Flanagan AM. Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nat Genet. 2011 Nov 6;43(12):1262-5. doi: 10.1038/ng.994. Citation on PubMed
• Herget GW, Strohm P, Rottenburger C, Kontny U, Krauss T, Bohm J, Sudkamp N, Uhl M. Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up. Neoplasma. 2014;61(4):365-78. doi: 10.4149/neo_2014_046. Citation on PubMed
• Pansuriya TC, Kroon HM, Bovee JV. Enchondromatosis: insights on the different subtypes. Int J Clin Exp Pathol. 2010 Jun 26;3(6):557-69. Citation on PubMed or Free article on PubMed Central
• Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovee JV. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet. 2011 Nov 6;43(12):1256-61. doi: 10.1038/ng.1004. Citation on PubMed or Free article on PubMed Central
• Silve C, Juppner H. Ollier disease. Orphanet J Rare Dis. 2006 Sep 22;1:37. doi: 10.1186/1750-1172-1-37. Citation on PubMed or Free article on PubMed Central
• Superti-Furga A, Spranger J, Nishimura G. Enchondromatosis revisited: new classification with molecular basis. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):154-64. doi: 10.1002/ajmg.c.31331. Epub 2012 Jul 12. Citation on PubMed
• Verdegaal SH, Bovee JV, Pansuriya TC, Grimer RJ, Ozger H, Jutte PC, San Julian M, Biau DJ, van der Geest IC, Leithner A, Streitburger A, Klenke FM, Gouin FG, Campanacci DA, Marec-Berard P, Hogendoorn PC, Brand R, Taminiau AH. Incidence, predictive factors, and prognosis of chondrosarcoma in patients with Ollier disease and Maffucci syndrome: an international multicenter study of 161 patients. Oncologist. 2011;16(12):1771-9. doi: 10.1634/theoncologist.2011-0200. Epub 2011 Dec 6. Citation on PubMed or Free article on PubMed Central