FaCD Online Syndrome Fact Sheet

Last updated: 29 Nov 2011

Name: Ollier disease / Maffuci syndrome

Synonym: Osteochondromatosis, Enchondromatosis

Mode of Inheritance: AD?/ spor

OMIM number: 166000  


IDH1, mapped to 2q34
IDH2, mapped to 15q26.1
PTHR1, mapped to 3p22-21.1

Tumor features

(spindle cell) hemangioendothelioma
gliomatosis cerebri
osteochondroma (enchondroma)
ovarian germ cell tumor
ovarian granulosa cell tumor
pituitary adenoma
subcutaneous hemangioma

Tumor features (possible)

adrenal adenoma
biliary tract cancer (incl. gallbladder)
hepatocellular cancer (hepatoma)
leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
leukemia, chronic myeloid (CML)
lung/bronchial cancer
neuroblastoma, extra-adrenal
ovarian teratoma
pancreatic adenocarcinoma

Non-tumor features

skeletal anomalies


Clinical hallmarks are multiple exostoses of the enchondromatous type, often dysplasia of epiphyseal cartilage sometimes resulting in long bone growth retardation, and hemangiomas/hemangioendotheliomas. The combination with these bloodvessel anomalies is referred to as Maffuci syndrome, vascular oral-gastrointestinal lesions are very rare[1]).

Patients are at risk to develop chondrosarcomas, sometimes of the dedifferentiated type[2]. Some patients develop multiple chondrosarcomas[9]. The frequency of sarcomatous degeneration has been estimated at 15-20% and is possibly lower in Ollier disease. A range of non-skeletal tumors has been reported, particularly in patients with Maffuci syndrome[3;4], although patients with Ollier disease may be more prone to intracranial neoplasms (gliomas, pituitary adenoma, neuroma and chordoma [5-7,10,18,19,22,23]). The association between enchondromatosis and these intracranial tumors malignancy appear to be roughly the same in youths versus adults, although Ollier's disease cases were seen more often among youths[17]. Another tumor reported in Ollier disease[8] is the ovarian Sertoli-Leydig cell tumor. Ollier and Maffuci patients may develop ovarian juvenile granulosa cell tumors[6,11-13]. A olfactory neuroblastoma was reported in a 33-year-old male with Maffuci syndrome[14]. Non-small cell lung cancer was diagnosed in a 44-year-old man with Ollier disease[15]. A few cases of leukemia (CML, ALL and AML) have been reported in Ollier patients[16].

Most cases are sporadic, however, a few familial cases of Ollier disease have been reported (autosomal dominant with reduced penetrance?). PTHR1 mutations are uncommon in Ollier/Maffuci; most cases are caused by postzygotic IDH1 or IDH2 mutations[20,21].


[1] Lee NH, Choi EH, Choi WK, Lee SH, Ahn SK. Maffucci's syndrome with oral and intestinal haemangioma [letter]. Br J Dermatol 1999; 140(5):968-969.
[2] Kilpatrick SE, Pike EJ, Ward WG, Pope TL. Dedifferentiated chondrosarcoma in patients with multiple osteochondromatosis: report of a case and review of the literature. Skeletal Radiol 1997; 26(6):370-374.
[3] Albregts AE, Rapini RP. Malignancy in Maffucci's syndrome. Dermatol Clin 1995; 13(1):73-78.
[4] Perkins P, Weiss SW. Spindle cell hemangioendothelioma: an analysis of 78 cases with reassessment of its pathogenesis and biologic behavior. Am J Surg Pathol 1996; 20(10):1196-1204.
[5] Frappaz D, Ricci AC, Kohler R, Bret P, Mottolese C. Diffuse brain stem tumor in an adolescent with multiple enchondromatosis (Ollier's disease). Childs Nerv Syst 1999; 15(5):222-225.
[6] Vaz RM, Turner C. Ollier disease (enchondromatosis) associated with ovarian juvenile granulosa cell tumor and precocious pseudopuberty. J Pediat 1986; 108(6):945-947.
[7] Kimmel DW, Cheng TM, Mokri B. Primary intracranial neoplasms in Ollier's disease. anonymous 1999;(P212):162.
[8] Weyl-Ben Arush M, Oslander L. Ollier's disease associated with ovarian sertoli-leydig cell tumor and breast adenoma. Am J Ped Hematol Oncol 1991; 13(1):49-51.
[9] Kosaki N, Yabe H, Anazawa U, Morioka H, Mukai M, Toyama Y. Bilateral multiple malignant transformation of Ollier's disease. Skeletal radiology 2005; 34(8):477-84.
[10] Mahafza WS. Multiple enchondromatosis Ollier's disease with two primary brain tumors. Saudi medical journal 2004; 25(9):1261-3.
[11] Yuan JQ, Lin XN, Xu JY, Zhu J, Zheng WL. Ovarian juvenile granulosa cell tumor associated with Maffucci's syndrome: case report. Chinese medical journal 2004; 117(10):1592-4.
[12] Hachi H, Othmany A, Douayri A, Bouchikhi C, Tijami F, Laâlou L, Chami M, Boughtab A, Jalil A, Benjelloun S, Ahyoud F, Kettani F, Souadka A. [Association of ovarian juvenile granulosa cell tumor with Maffucci's syndrome]. Gynécologie, obstétrique & fertilité 2002; 30(9):692-5.
[13] Velasco-Oses A, Alonso-Alvaro A, Blanco-Pozo A, Nogales FF. Ollier's disease associated with ovarian juvenile granulosa cell tumor. Cancer 1988; 62(1):222-5.
[14] Kurian S, Ertan E, Ducatman B, Crowell EB, Rassekh C. Esthesioneuroblastoma in Maffucci's syndrome. Skeletal radiology 2004; 33(10):609-12.
[15] Sendur OF, Turan Y, Odabasi BB, Berkit IK. A case of Ollier disease with non-small cell lung cancer and review of the literature. Rheumatol Int. 2009 Jun 6. [Epub ahead of print]
[16] White MS, Martin PL, McLean TW. Acute myelogenous leukemia associated with Ollier disease. Pediatr Blood Cancer. 2008 Mar;50(3):645-6.
[17] Ranger A, Szymczak A. The association between intracranial tumours and multiple dyschondroplasia (Ollier's disease or Maffucci's syndrome): do children and adults differ? J Neurooncol. 2009 Jun 9. [Epub ahead of print]
[18] Ruivo J, Antunes JL. Maffucci syndrome associated with a pituitary adenoma and a probable brainstem tumor. J Neurosurg. 2009 Feb;110(2):363-8.
[19] Walid MS, Troup EC. Cerebellar anaplastic astrocytoma in a teenager with Ollier Disease. J Neurooncol. 2008 Aug;89(1):59-62.
[20] 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. doi: 10.1038/ng.994. [Epub ahead of print]
[21] 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, Bovée 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. doi: 10.1038/ng.1004. [Epub ahead of print]
[22] Mitchell RA et al. Gliomatosis cerebri in a patient with Ollier disease. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2011; 18:1564-6.
[23] Ranger A et al. Do intracranial neoplasms differ in Ollier disease and maffucci syndrome? An in-depth analysis of the literature. Neurosurgery 2009; 65:1106-13; discussion 1113-5.