Multiple Epiphyseal Dysplasia

Reference work entry

In 1945, Fairbank first described multiple epiphyseal dysplasia (MED). MED is a type of short-limbed dwarfism characterized by impaired endochondral ossification affecting multiple epiphyses and premature degenerative joint disease.

Synonyms and Related Disorders

Autosomal dominant multiple epiphyseal dysplasia (Fairbank type, Ribbling type); Autosomal recessive multiple epiphyseal dysplasia (with bilayered patellae, with clubfoot)

Genetics/Basic Defects

  1. 1.
    Inheritance: genetically heterogeneous
    1. a.
      Autosomal dominant (Briggs et al. 2011)
      1. i.

        Multiple epiphyseal dysplasia type I (EDM1)

      2. ii.

        Multiple epiphyseal dysplasia type II (EDM2)

      3. iii.

        Multiple epiphyseal dysplasia type III (EDM3)

      4. iv.

        Multiple epiphyseal dysplasia type V (EDM5)

      5. v.

        Multiple epiphyseal dysplasia type VI (EDM6)

    2. b.

      Autosomal recessive: multiple epiphyseal dysplasia type IV (EDM4)

  2. 2.
    1. a.

      EDM1: mutations in the gene (COMP) encoding cartilage oligomeric matrix protein (COMP) on the centromeric region...


Club Foot Cartilage Oligomeric Matrix Protein Ossification Center Cartilage Oligomeric Matrix Protein Distinctive Clinical Feature 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ballo, R., Briggs, M. D., Cohn, D. H., et al. (1997). Multiple epiphyseal dysplasia. Ribbing type: A novel point mutation in the COMP gene in a South African family. American Journal of Medical Genetics, 68, 396–400.PubMedCrossRefGoogle Scholar
  2. Berg, P. K. (1966). Dysplasia epiphysialis multiplex: A case report and review of the literature. American Journal of Roentgenology, 97, 31–38.Google Scholar
  3. Bonafé, L., Mittaz-Crettol, L., & Ballhausen, D. (2010). Multiple epiphyseal dysplasia, recessive. GeneReviews. Retrieved March 18, 2010.
  4. Briggs, M. D., Hoffman, S. M. G., King, L. M., et al. (1995). Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Nature Genetics, 10, 330–336.PubMedCrossRefGoogle Scholar
  5. Briggs, M. D., Mortier, G. R., Cole, W. G., et al. (1998). Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum. American Journal of Human Genetics, 62, 311–319.PubMedCrossRefGoogle Scholar
  6. Briggs, M. D., Wright, M. J., & Mortier, G. R. (2011). Multiple epiphyseal dysplasia, dominant. GeneReviews. Retrieved February 1, 2011. Available at:
  7. Chapman, K. L., Briggs, M. D., & Mortier, G. R. (2003). Review: Clinical variability and genetic heterogeneity in multiple epiphyseal dysplasia. Pediatric Pathology & Molecular Medicine, 22, 53–75.CrossRefGoogle Scholar
  8. Cho, T.-J., Kim, O.-H., Lee, H.-R., et al. (2010). Autosomal recessive multiple epiphyseal dysplasia in a Korean girl caused by novel compound heterozygous mutations in the DTDST (SLC26A2) gene. Journal of Korean Medical Science, 25, 1105–1108.PubMedCrossRefGoogle Scholar
  9. Czarny-Ratajczak, M., Lohiniva, J., Rogala, P., et al. (2001). A mutation in COL9A1 causes multiple epiphyseal dysplasia. Further evidence for locus heterogeneity in MED. American Journal of Human Genetics, 69, 969–980.PubMedCrossRefGoogle Scholar
  10. Deere, M., Blanton, S. H., Scott, C. I., et al. (1995). Genetic heterogeneity in multiple epiphyseal dysplasia. American Journal of Human Genetics, 56, 698–704.PubMedGoogle Scholar
  11. Deere, M., Sanford, T., Francomano, C., et al. (1999). Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia. American Journal of Medical Genetics, 85, 486–490.PubMedCrossRefGoogle Scholar
  12. Fairbank, H. A. T. (1945). Dysplasia epiphysealis multiplex. Proceedings of the Royal Society of Medicine, 39, 315–317.Google Scholar
  13. Hinrichs, T., Superti-Furga, A., Scheiderer, W.-D., et al. (2010). Recessive multiple epiphyseal dysplasia (rMED) with homozygosity for C653S mutation in the DTDST gene – Phenotype, molecular diagnosis and surgical treatment of habitual dislocation of multilayered patella: Case report. BMC Musculoskeletal Disorders, 11, 110–115.PubMedCrossRefGoogle Scholar
  14. Hoefnagel, D., Sycamore, L. K., Russell, S. W., et al. (1967). Hereditary multiple epiphysial dysplasia. Annals of Human Genetics, 30, 201–210.PubMedCrossRefGoogle Scholar
  15. Hunt, D. D., Ponseti, I. V., Pedrini-Mille, A., et al. (1967). Multiple epiphyseal dysplasia in two siblings. Journal of Bone and Joint Surgery, 49A, 1611–1627.Google Scholar
  16. Ikegawa, S., Ohashi, H., Nishimura, G., et al. (1998). Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple metaphyseal dysplasia. Human Genetics, 103, 633–638.PubMedCrossRefGoogle Scholar
  17. Jacobs, P. A. (1968). Dysplasia epiphysialis multiplex. Clinical Orthopaedics, 58, 117–128.CrossRefGoogle Scholar
  18. Leeds, N. E. (1960). Epiphysial dysplasia multiplex. American Journal of Roentgenology, 84, 506–510.Google Scholar
  19. Mäkitie, O., Mortier, G. R., Czarny-Ratajczak, M., et al. (2004). Clinical and radiographic findings in multiple epiphyseal dysplasia caused by MATN3 mutations: Description of 12 patients. American Journal of Medical Genetics, 125A, 278–284.PubMedCrossRefGoogle Scholar
  20. Maudsley, R. H. (1955). Dysplasia epiphysialis multiplex: A report of fourteen cases in three families. Journal of Bone and Joint Surgery, 37B, 228–240.Google Scholar
  21. Miyake, A., Nishimura, G., Futami, T., et al. (2008). A compound heterozygote of novel and recurrent DTDST mutations results in a novel intermediate phenotype of Desbuquois dysplasia, diastrophic dysplasia, and recessive form of multiple epiphyseal dysplasia. Journal of Human Genetics, 53, 764–768.PubMedCrossRefGoogle Scholar
  22. Mortier, G. R., Chapman, K., Leroy, J. L., et al. (2001). Clinical and radiographic features of multiple epiphyseal dysplasia not linked to the COMP or type IX collagen genes. European Journal of Human Genetics, 9, 606–612.PubMedCrossRefGoogle Scholar
  23. Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., et al. (1996). A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2). Nature Genetics, 12, 103–105.PubMedCrossRefGoogle Scholar
  24. Murphy, M. C., Shine, I., & Stevens, D. B. (1973). Multiple epiphyseal dysplasia: Report of a pedigree. Journal of Bone and Joint Surgery, 55A, 814–820.Google Scholar
  25. Oehlmann, R., Summerville, G. P., Yeh, G., et al. (1994). Genetic linkage mapping of multiple epiphyseal dysplasia to the pericentromeric region of chromosome 19. American Journal of Human Genetics, 54, 3–10.PubMedGoogle Scholar
  26. Paassilta, P., Lohiniva, J., Annunen, S., et al. (1999). COL9A3: A third locus for multiple epiphyseal dysplasia. American Journal of Human Genetics, 64, 1036–1044.PubMedCrossRefGoogle Scholar
  27. Sheffield, E. G. (1998). Double-layered patella in multiple epiphyseal dysplasia: A valuable clue in the diagnosis. Journal of Pediatric Orthopedics, 18, 123–128.PubMedCrossRefGoogle Scholar
  28. Stanescu, R., Stanescu, V., Muriel, M.-P., et al. (1993). Multiple epiphyseal dysplasia, Fairbank type: Morphologic and biochemical study of cartilage. American Journal of Medical Genetics, 45, 501–507.PubMedCrossRefGoogle Scholar
  29. Superti-Furga, A., Neumann, L., Riebel, T., et al. (1999). Recessively inherited multiple epiphyseal dysplasia with normal stature, clubfoot, and double layered patella caused by a DTDST mutation. Journal of Medical Genetics, 36, 621–624.PubMedGoogle Scholar
  30. Superti-Furga, A., Spbetzko, D., Hecht, J. T., et al. (2000). Recessive multiple epiphyseal dysplasia (rMED: MIM 226900): Phenotype delineation in twelve individuals homozygous for DTST mutation R279W. American Journal of Human Genetics, 67(Suppl. 2), 379.Google Scholar
  31. Thornton, C. M., Carson, D. J., & Stewart, F. J. (1997). Autopsy findings in the Wolcott–Rallison syndrome. Pediatric Pathology & Laboratory Medicine, 17, 487–496.CrossRefGoogle Scholar
  32. Unger, S., Bonafé, L., & Superti-Furga, A. (2008). Multiple epiphyseal dysplasia: Clinical and radiographic features, differential diagnosis and molecular basis. Best Practice & Research. Clinical Rheumatology, 22, 19–32.CrossRefGoogle Scholar
  33. Unger, S. L., Briggs, M. D., Holden, P., et al. (2001). Multiple epiphyseal dysplasia: Radiographic abnormalities correlated with genotype. Pediatric Radiology, 31, 10–18.PubMedCrossRefGoogle Scholar
  34. Unger, S., & Hecht, J. T. (2001). Pseudoachondroplasia and multiple epiphyseal dysplasia: New etiologic developments. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 106, 244–250.CrossRefGoogle Scholar
  35. Villarreal, T., Carnevale, A., Mayen, D. G., et al. (1992). Anthropometric studies in five children and their mother with a severe form multiple epiphyseal dysplasia. American Journal of Medical Genetics, 42, 415–419.PubMedCrossRefGoogle Scholar
  36. Watt, J. K. (1952). Multiple epiphyseal dysplasia: Report of four cases. British Journal of Surgery, 39, 533–535.PubMedCrossRefGoogle Scholar
  37. Waugh, W. (1952). Dysplasia epiphysialis multiplex in three sisters. Journal of Bone and Joint Surgery, 34B, 82–87.Google Scholar

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