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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Medical Genetics

The Biology of a 'Glitch': Genetics and Diagnosis

At a Glance

Ollier disease is a non-inherited condition caused by a random genetic mutation (somatic mosaicism) in the IDH1 or IDH2 genes after conception. This mutation causes cartilage cells to form benign bone tumors called enchondromas, which require lifelong monitoring with whole-body MRIs.

To understand Ollier disease, it helps to look deep inside the body’s cells at the genetic level. This condition is not something you are born with because of your parents’ genes; rather, it is the result of a biological “glitch” that happens early in development.

The Concept of Somatic Mosaicism

Most genetic conditions are “germline,” meaning the mutation is in every cell of the body and can be passed from parent to child. Ollier disease is different. It is caused by somatic mosaicism [1][2].

Think of the body like a tiled floor. In a typical person, every tile is the same color. In someone with Ollier disease, a random mutation occurs in a single cell shortly after conception [1]. As that cell divides, it creates a “patch” of cells with the mutation, while the rest of the body remains unaffected. Because this change happened after the egg was fertilized, it is not hereditary—you did not inherit it from your parents, and you cannot pass it on to your children [1][3].

The Role of IDH Mutations and D-2HG

The “glitch” in Ollier disease usually occurs in the IDH1 or IDH2 genes [4][5]. These genes are responsible for producing enzymes that help cells create energy. When they are mutated, they start doing a “new” job: producing a substance called D-2-hydroxyglutarate (D-2HG) [6][7].

D-2HG is known as an oncometabolite [8]. Its presence essentially blocks the “off switches” that tell cartilage cells to stop growing and turn into bone [7][9]. Instead of maturing normally, these cells get stuck in an immature state, piling up inside the bones to form enchondromas (benign cartilage tumors) [7][10].

Ollier Disease vs. Maffucci Syndrome

While Ollier disease is the most common form of multiple enchondromatosis, it is often confused with Maffucci syndrome. The difference is found in the soft tissues:

  • Ollier Disease: Characterized by multiple enchondromas in the bones [11][12].
  • Maffucci Syndrome: Characterized by multiple enchondromas plus hemangiomas [11][12]. These are benign, blue-red growths made of tangled blood vessels that appear under the skin or in soft tissues [13][11].

Distinguishing between the two is important because Maffucci syndrome may carry a higher risk of certain types of cancer and requires its own specific monitoring schedule [13][14].

Diagnostic Imaging

Diagnosis is primarily made through specialized imaging that allows doctors to see the “map” of the disease:

  1. Plain X-rays: These are the first step. Enchondromas appear as well-defined, “hollowed-out” areas (osteolytic lesions) near the ends of the long bones [15][16].
  2. Baseline Whole-Body MRI: Current consensus among experts is to perform a baseline whole-body MRI [17][14]. This provides a master map of every lesion in the body, which is essential for future comparisons. If a lesion starts to grow rapidly or causes new pain, doctors can look back at this “baseline” to see exactly how much it has changed [17][18].
  3. Surveillance: Because there is a lifetime risk of malignant transformation into chondrosarcoma (estimated between 5% and 50%, varying by disease severity), regular imaging is the standard of care for early detection. The frequency of this imaging will be determined by your specialist [12][16].

Common questions in this guide

Is Ollier disease inherited from my parents?
No, Ollier disease is not inherited. It is caused by somatic mosaicism, meaning a random genetic mutation occurs in a single cell shortly after conception. Because it happens after fertilization, you did not inherit it from your parents, and you cannot pass it to your children.
What is the difference between Ollier disease and Maffucci syndrome?
Both conditions involve multiple benign bone tumors called enchondromas. However, Maffucci syndrome also includes hemangiomas, which are benign, blue-red blood vessel growths found under the skin or in soft tissues. It is important to distinguish between the two because Maffucci syndrome may carry a higher risk of certain cancers.
What causes enchondromas to form in Ollier disease?
Mutations in the IDH1 or IDH2 genes cause cells to produce a substance called D-2-hydroxyglutarate (D-2HG). This substance essentially breaks the 'off switches' that tell cartilage cells to mature into bone. Instead, the cells get stuck in an immature state and pile up to form benign tumors.
Why do I need a baseline whole-body MRI for Ollier disease?
A baseline whole-body MRI creates a master map of all existing bone lesions in the body. This provides an essential reference point, allowing your medical team to monitor the tumors over time and quickly identify if any begin to grow rapidly or change into cancer.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Can you explain if my child has a mutation in IDH1 or IDH2, and how that specific mutation affects their monitoring?
  2. 2.What is the standard protocol at this hospital for a baseline whole-body MRI, and how often will it be repeated?
  3. 3.If we see new 'spots' or hemangiomas on the skin, does that change the diagnosis from Ollier to Maffucci syndrome?
  4. 4.How do the radiologists at this center differentiate between a stable enchondroma and early-stage chondrosarcoma on MRI?
  5. 5.Given the risk of non-skeletal tumors like gliomas, should we be doing any baseline brain imaging?

Questions For You

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References

References (18)
  1. 1

    Gene of the month: IDH1.

    Bruce-Brand C, Govender D

    Journal of clinical pathology 2020; (73(10)):611-615 doi:10.1136/jclinpath-2020-206813.

    PMID: 32727816
  2. 2

    Molecular profiling of different glioma specimens from an Ollier disease patient suggests a multifocal disease process in the setting of IDH mosaicism.

    Tan CL, Vellayappan B, Wu B, et al.

    Brain tumor pathology 2018; (35(4)):202-208 doi:10.1007/s10014-018-0327-y.

    PMID: 30159860
  3. 3

    Maffucci syndrome complicated by three different central nervous system tumors sharing an IDH1 R132C mutation: case report.

    Nejo T, Tanaka S, Ikemura M, et al.

    Journal of neurosurgery 2019; (131(6)):1829-1834 doi:10.3171/2018.6.JNS18729.

    PMID: 30579273
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    Enchondromatosis-associated oligodendroglioma: case report and literature review.

    Achiha T, Arita H, Kagawa N, et al.

    Brain tumor pathology 2018; (35(1)):36-40 doi:10.1007/s10014-017-0303-y.

    PMID: 29224049
  5. 5

    IDH Mutations Are Potentially the Intrinsic Genetic Link among the Multiple Neoplastic Lesions in Ollier Disease and Maffucci Syndrome: A Clinicopathologic Analysis from a Single Institute in Shanghai, China.

    Chen C, Li J, Jiang T, et al.

    Diagnostics (Basel, Switzerland) 2022; (12(11)) doi:10.3390/diagnostics12112764.

    PMID: 36428825
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    Isocitrate Dehydrogenase Mutation and (R)-2-Hydroxyglutarate: From Basic Discovery to Therapeutics Development.

    Dang L, Su SM

    Annual review of biochemistry 2017; (86()):305-331 doi:10.1146/annurev-biochem-061516-044732.

    PMID: 28375741
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    Quantitative Analysis of Oncometabolite 2-Hydroxyglutarate.

    Yuan BF

    Advances in experimental medicine and biology 2021; (1280()):161-172 doi:10.1007/978-3-030-51652-9_11.

    PMID: 33791981
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    Identification of Isocitrate Dehydrogenase 2 (IDH2) Mutation in Carotid Body Paraganglioma.

    Lang F, Jha A, Meuter L, et al.

    Frontiers in endocrinology 2021; (12()):731096 doi:10.3389/fendo.2021.731096.

    PMID: 34616365
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    2-hydroxyglutarate inhibits MyoD-mediated differentiation by preventing H3K9 demethylation.

    Schvartzman JM, Reuter VP, Koche RP, Thompson CB

    Proceedings of the National Academy of Sciences of the United States of America 2019; (116(26)):12851-12856 doi:10.1073/pnas.1817662116.

    PMID: 31182575
  10. 10

    Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

    Li L, Paz AC, Wilky BA, et al.

    PloS one 2015; (10(9)):e0133813 doi:10.1371/journal.pone.0133813.

    PMID: 26368816
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    IDH1 R132C and ERC2 L309I Mutations Contribute to the Development of Maffucci's Syndrome.

    Cheng P, Chen K, Zhang S, et al.

    Frontiers in endocrinology 2021; (12()):763349 doi:10.3389/fendo.2021.763349.

    PMID: 34790172
  12. 12

    Update on the imaging features of the enchondromatosis syndromes.

    Sharif B, Lindsay D, Saifuddin A

    Skeletal radiology 2022; (51(4)):747-762 doi:10.1007/s00256-021-03870-0.

    PMID: 34302201
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    Maffucci Syndrome. An Interesting Case and a Review of the Literature.

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    Bulletin of the Hospital for Joint Disease (2013) 2015; (73(4)):282-5.

    PMID: 26630472
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    Maffucci Syndrome with Clival Enchondroma in Nasopharynx: A Case Report.

    Velagapudi S, Alshammari SM, Velagapudi S

    Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India 2019; (71(Suppl 1)):652-656 doi:10.1007/s12070-018-1463-8.

    PMID: 31742037
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    Ollier Disease: Pathogenesis, Diagnosis, and Management.

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    Orthopedics 2015; (38(6)):e497-506 doi:10.3928/01477447-20150603-58.

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    Ollier Disease: A Case Series and Literature Review.

    Markevičiūtė V, Markevičiūtė MŠ, Stravinskas M

    Acta medica Lituanic 2021; (28(1)):181-188 doi:10.15388/Amed.2021.28.1.8.

    PMID: 34393643
  17. 17

    Update on Cancer Screening in Children with Syndromes of Bone Lesions, Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome, and Other Rare Syndromes.

    Michaeli O, Kim SY, Mitchell SG, et al.

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    MRI features of low-grade and high-grade chondrosarcoma in enchondromatosis.

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    PMID: 33484272

This page provides educational information about the genetics and diagnosis of Ollier disease. It is not a substitute for professional medical advice, diagnosis, or screening recommendations from your healthcare provider.

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