Ollier Disease

Disease Overview

Summary

Ollier disease is a rare skeletal disorder characterized by abnormal bone development (skeletal dysplasia). While this disorder may be present at birth (congenital), it may not become apparent until early childhood when symptoms such as deformities or improper limb growth are more obvious. Ollier disease primarily affects the long bones and cartilage of the joints of the arms and legs, specifically the area where the shaft and head of a long bone meet (metaphyses). The pelvis is often involved; and more rarely, the ribs, breast bone (sternum), and/or skull may also be affected.

Ollier disease manifests as greater than normal growth of the cartilage in the long bones of the legs and arms so that growth is abnormal and the outer layer (cortical bone) of the bone becomes thin and more fragile. These masses of cartilage are benign (non-cancerous) tumors known as enchondromas. Enchondromas may occur at any time. In about 30% of patients, the enchondromas may undergo malignant changes to a cancer such as chondrosarcomas. Malignant transformation is more likely to occur in the long tubular and flat bones.

Introduction

There are seven major subtypes of enchondromas: the most common are Ollier disease (subtype I) and Maffucci syndrome (subtype II). When the enchondromas are accompanied by substantial, most often benign, proliferation of blood vessels (vascular anomalies), the array of symptoms is known as Maffucci syndrome. The others are metachondromatosis, genochondromatosis, spondyloenchondrodysplasia, dysspondyloenchondromatosis and cheirospondyloenchondromatosis. The classification of subtypes is based on how the disease affects the patient, whether or not the spine is involved, and the pattern of inheritance.

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Synonyms

• dyschondroplasia
• enchondromatosis
• multiple cartilaginous enchondroses
• multiple enchondromatosis

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Signs & Symptoms

Ollier disease is not always apparent at birth, but symptoms will usually become evident by early childhood. Between the ages of one and four years, abnormal and/or slow growth of arms and legs is often observed. Usually one leg and/or arm is affected, but both legs and/or arms may be involved. If both legs are involved, short stature may result; if only one leg is involved, then an affected individual may limp.

The pelvis is sometimes involved and rarely, the ribs, breast bone (sternum), and/or skull may be affected. Deformities may also develop in the wrists and ankles. Limb shortening and bowing of the long bones may occur in some affected individuals.

Ollier disease also hampers proper development of bone (ossification). Fractures are a common occurrence in people affected by this disorder and usually heal well. In some patients, the development of some forms of malignant bone growths has been associated with Ollier disease.

Other rare complications can arise, such as gliomas and juvenile granulosa cell tumors. Gliomas are a type of brain tumor; they are referred to as intra-axial brain tumors, which refer to the growth of the brain tumors within the brain tissue itself. Juvenile granulosa cell tumor (JGCT) is a rare ovarian cancer; it has a favorable prognosis if diagnosed early.

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Causes

The underlying cause of Ollier disease is not known. Changes (mutations) in IDH1, IDH2 and PTHR1 genes have been linked to Ollier disease and Maffucci syndrome. The mutations are due to somatic mosaicism, which means that the mutation is present only in a percentage of the cells, not all the cells in the body. In Ollier disease, the mutation is present only in the enchondromas.

So far, all the cases of Ollier disease have been sporadic in their families and not inherited. But, in theory, if a gene mutation is present in the egg or sperm (germline), the condition could be passed on in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a de novo mutated (changed) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

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Affected populations

The estimated prevalence of the disease is 1/100,000. Ollier disease is a very rare disorder that affects males and females in equal numbers. Symptoms are most often observed in children but can occur in adolescents and adults. This disorder can affect all races.

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Disorders with Similar Symptoms

Symptoms of the following disorders can be similar to those of Ollier disease. Comparisons may be useful for a differential diagnosis:

Metachondromatosis presents with enchondromas and osteochondroma (exostoses). The enchondromas most commonly involve the long bones of the legs and the hip. The osteochondroma lesions usually appear on the hands and feet. Most of the time, these lesions do not cause bone deformities. There are less than 30 reported cases currently.

Genochondromatosis is an extremely rare autosomal dominant disorder. Patients have normal stature and enchondromas are distributed symmetrically with characteristic localization in the metaphyses of the upper part of the arms (proximal humerus) and lower part of the thigh bone (distal femur). Two subtypes are distinguished: genochondromatosis type I includes the presence of a enchondromas on the inner side (medial side) of the clavicle, while in type II the short tubular bones of the hand, wrist and feet are affected while the clavicle is normal.

Spondyloenchondrodysplasia (SPENCD, enchondromatosis Spranger type IV) is an autosomal recessive inherited disorder caused by mutations in the ACP5 gene. It is characterized by vertebral dysplasia combined with enchondroma like lesions in the pelvis or long tubular bones.

Dysspondyloenchondromatosis is a nonhereditary skeletal dysplasia characterized by abnormally varying sizes of verterbral bodies (anisospondyly), which comprise the bones of the spine, and multiple enchondromas in vertebrae and the metaphyseal and diaphyseal parts of long tubular bones, leading to kyphoscoliosis and lower limb asymmetry.

Cheirospondyloenchondromatosis (generalized enchondromatosis with platyspondyly, enchondromatosis Spranger type VI) combines symmetrically distributed multiple enchondromas with marked involvement of metacarpals and phalanges resulting in short hands and feet with mild flattening of the vertebral bodies of the spine (platyspondyly). It occurs at a very early age. There is mild to moderate dwarfism and joints, especially of the fingers, become enlarged. In addition, intellectual disability is frequently associated with this disease.

Maffucci syndrome is a rare genetic disorder characterized by enchondromas, skeletal deformities, and dark red irregularly shaped patches of skin, resulting from benign growths on the skin (cutaneous) consisting of masses of blood vessels (vascular anomalies). Enchondromas are most often found in certain bones (phalanges) of the hands and feet. Skeletal malformations may include legs that are disproportionate in length and/or abnormal side-to-side curvature of the spine (scoliosis). In many patients, bones may tend to fracture easily. In most patients, hemangiomas appear at birth or during early childhood and may be progressive. Maffucci syndrome is also a sporadic disease and no inherited cases have been reported so far. (For more information on this disorder, choose “Maffucci” as your search term in the Rare Disease Database).

Hereditary multiple osteochondromas (HMO) is a rare genetic disorder characterized by multiple benign (noncancerous) bone tumors that are covered by cartilage (osteochondromas), often on the growing end (metaphysis) of the long bones of the legs, arms, and digits. These osteochondromas usually continue to grow until shortly after puberty and may lead to bone deformities, skeletal abnormalities, short stature, nerve compression and reduced range of motion. Hereditary multiple osteochondromas is inherited as an autosomal dominant genetic condition and is associated with mutations in the EXT1 or EXT2 genes. (For more information on this disorder, choose “hereditary multiple osteochondromas” as your search term in the Rare Disease Database).

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Diagnosis

Methods of diagnosing Ollier disease include bone biopsy, x-rays, magnetic resonance imaging (MRI), and recording of internal body images (tomography). Affected individuals should be checked routinely by a physician for malignant changes in the bones and joints (e.g., chondrosarcoma).

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Standard Therapies

Treatment
Surgical correction of deformities of the affected limb(s) has been helpful. In severe cases, artificial (prosthetic) joint replacement may become necessary. Fractures routinely heal without complications. A supportive team approach for children with Ollier disease may be of benefit. Such a team approach may include physical therapy and other medical, social, or vocational services. Other treatment is symptomatic and supportive.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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References

TEXTBOOKS
Jones KL, ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:519.

Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1390.

Fauci AS, et al., eds. Harrison’s Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:2274.

Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Central Role of Enzymes as Biological Catalysts

JOURNAL ARTICLES
Wang J P, Xu Z Y, Bao Z Q, et al. Ollier disease: two case reports and a review of the literature. American journal of translational research 2018; 10(11);3818-3826.

Burgetova A, Matejovsky Z, Zikan M, et al. The association of enchondromatosis with malignant transformed chondrosarcoma and ovarian juvenile granulosa cell tumor (Ollier disease). Taiwanese Journal of Obstetrics and Gynecology 2017;56(2): 253-257.

Kumar A, Jain VK, Bharadwaj M, Arya RK. Ollier Disease: Pathogenesis, Diagnosis, and Management. Orthopedics. 2015 Jun; 38(6):e497-506.

Freed D, Stevens E L and Pevsner J. Somatic mosaicism in the human genome. Genes 2014; 5(4):1064-94.

Pansuriya T C, 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. Nature genetics 2011; 43(12): 1256-61.

Vázquez-García B, Valverde M, and San-Julián M. Ollier’s disease: Benign tumors with risk of malignancy. Review of 17 cases. Anales De Pediatría 2011;74(3):168-173.

Hori K, Matsumine A, Niimi R, et al. Diffuse gliomas in an adolescent with multiple enchondromatosis (Ollier’s disease). Oncology Letters 2010; 1(4): 595-597.

Pansuriya TC, Kroon H M, and Bovée JV. Enchondromatosis: insights on the different subtypes. International Journal of Clinical and Experimental Pathology 2010; 3(6): 557-69.

INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 166000; Last Update:05/02/2016. https://www.omim.org/entry/166000 Accessed Feb 12, 2020.

Chew FS. Medscape. Enchondroma and Enchondromatosis Imaging. Updated: Jan 24, 2018 Retrieved from https://emedicine.medscape.com/article/389224-overview Accessed Feb 12, 2020.

Spondyloenchondrodysplasia. Genetic and Rare Diseases Information Center. Last updated: 2/1/2016 Retrieved from https://rarediseases.info.nih.gov/diseases/4978/spondyloenchondrodysplasia Accessed Feb 12, 2020

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Programs & Resources

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Patient Organizations

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Related Rare Diseases: Chanarin-Dorfman Syndrome, Congenital Myasthenic Syndromes, Arterial Tortuosity Syndrome, ...

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More Information

The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.

GARD Disease Summary

The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).

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Orphanet

Orphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.

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OMIM

Online Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.

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