Multiple enchondromatosis, Ollier type

(OMIM phenotype number %166000)

Enchondromatosis is a rare heterogeneous skeletal disease characterized by multiple enchondromas, and it includes several different subtypes of which Ollier disease and Maffucci syndrome are most common. Enchondromas are benign hyaline cartilage forming tumors in the medulla of metaphyseal bone. Ollier disease (also known as dyschondroplasia, multiple cartilaginous enchondromatosis, en- chondromatosis Spranger type I) is characterized by multiple enchondromatosis with an asymmetric distribution. Lesions are usually distributed in the appendicular skeleton (the skull and vertebral bodies are very rarely involved). In particular, enchondromas are most commonly seen in phalanges and metacarpals and rarely in the carpal bones. However, there is a wide variety of presentations in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, and requirement for surgery. Clinical problems caused by enchondromas include skeletal deformities, limb-length discrepancy, and the potential risk for malignant change to chondrosarcoma. Malignant transformation of one or more enchondromas towards secondary central chondrosarcoma is estimated to occur in 5-50% of the patients. Radiologically, Ollier disease presents with asymmetrical osteolytic lesions with well-defined, sclerotic margins. Clinical manifestations of Ollier disease often manifests itself  in the first decade of life without any significant gender bias, but has also been reported in early adolescence and adulthood. The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci syndrome. The estimated prevalence of Ollier disease is 1/100.000. The pathogenesis of enchondromatosis is not clearly understood. Recently, heterozygous mutations of PTHR1, IDH1 (most common), and/or IDH2 genes have been suggested as genetic aberrations. The inheritance pattern of Ollier disease is unknown but is thought to not be simply a Mendelian pattern. The diagnosis is based on clinical and conventional radiological evaluations. Histological analysis has a limited role and is mainly used if malignancy is suspected. Ollier disease must be differentiated from multiple hereditary exostosis, and radiologically, Ollier disease may mimic osteitis fibrosa cystica.

There is no medical treatment for enchondromatosis, but treatment of Ollier disease is usually conservative. Surgery is performed in cases of complications and malignant transformation.

Gene

PTHR1 gene, 3p21.31 (OMIM gene/locus number *168468); IDH1 gene, 2q34 (OMIM gene/locus number *147700); IDH2 gene, 15q26.1 (OMIM gene/locus number *147650).

Phenotype

Soft tissue hemangiomas (Maffucci syndrome), multiple enchondromas with skeletal deformities and potential risk for malignant change to chondrosarcoma.

Main biochemical alterations

Slightly high PTH.

Images

Multiple enchondromatosis, Ollier type

Fig. (a) 4-year-old female patient with Ollier disease. Multiple enchondromas, manifesting as central end eccentric osteolytic lesions and deformities in the metacarpals and phalanges of the fourth and fifth ray of the right hand. (b) Same patient 13 years later. The enchondromas have increased in size and some are more evidently visible compared to the previous study. This has resulted in deformity of the fourth finger.

Reproduced from Pansuriya TC, Kroon HM, Bovée JV, Enchondromatosis: insights on the different subtypes. Int J Clin Exp Pathol 2010;3:557-69.

 

References
  1. Silve C, Jüppner H. Ollier disease. Orphanet J Rare Dis. 2006 Sep 22;1:37.
  2. Kumar A, Jain VK, Bharadwaj M, et al. Ollier Disease: Pathogenesis, Diagnosis, and Management. Orthopedics. 2015 Jun;38(6):e497-506.
  3. Pansuriya TC, Kroon HM, Bovée JV. Enchondromatosis: insights on the different subtypes. Int J Clin Exp Pathol. 2010 Jun 26;3(6):557-69.
  4. Hopyan S, Gokgoz N, Poon R, et al. A mutant PTH/PTHrP type I receptor in enchondromatosis. Nat Genet. 2002 Mar;30(3):306-10.
  5. Amary MF, Damato S, Halai D, et al. Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nat Genet. 2011 Nov 6;43(12):1262-5
  6. Pansuriya TC, van Eijk R, d'Adamo P, et al. 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
  7. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  8. http://www.omim.org