Multiple Epiphyseal Dysplasia

Updated: Aug 26, 2015
  • Author: Ashish S Ranade, MBBS, MS, MRCS; Chief Editor: Dennis P Grogan, MD  more...
  • Print
Overview

Background

In 1935, Thomas Fairbank described a patient with irregular ossification of multiple epiphyses. In 1947, he coined the term dysplasia epiphysealis multiplex and discussed its clinical and radiologic features. [1]  Currently, this condition is commonly referred to as multiple epiphyseal dysplasia (MED).

Among the osteochondrodysplasias, MED occurs most commonly. Studies suggest a prevalence of 9-16 cases per 100,000 births. [2, 3]  MED is characterized by involvement of multiple epiphyses with variable phenotypes. In general, MED is inherited in an autosomal dominant pattern; however, other inheritance forms are also seen. [4, 5, 6]

The goals of medical management of MED are to alleviate pain and to halt joint destruction and the development of early osteoarthritis. The goals of surgical therapy are pain relief, correction of angular deformities, and correction of joint contractures. Indications for surgical intervention to manage MED are pain, subluxation of the joint, and angular deformity. No specific guidelines about contraindications are available; contraindications to surgical intervention to treat MED are the same as those for any other planned surgical procedure.

Next:

Pathophysiology

Cartilage oligomeric matrix protein (COMP) and matrilin-3 (MATN3) are thought to bridge extracellular matrix proteins. Collagen IX is important for the adhesive properties of cartilage. Altered enchondral ossification may be associated with changes in the articular cartilage. The resultant articular cartilage is deficient in underlying osseous support and fails to withstand normal cyclical loading. [7, 8]

Studies have revealed the following genotypic-phenotypic correlations:

  • MED arising from COMP mutations is significantly associated with involvement of the proximal femur and acetabulum [9]
  • MED resulting from mutations affecting type IX collagen leads to severe involvement of the knees rather than the hips
  • Individuals with the recurrent R718W mutation in the COMP gene have a relatively mild form of MED [10]
  • MED arising from MATN3 mutations tends to have milder clinical manifestations than MED caused by  COMP mutations [11]
Previous
Next:

Etiology

The exact etiology of MED remains unclear. No potential causes or risk factors for MED are known. Genetic alterations result in abnormal enchondral ossification.

MED is a heterogeneous disorder. It can be caused by mutations in several genes, including the following [12, 13] :

  • COMP, which encodes COMP
  • COL9A1, COL9A2, and COL9A3, which encode type IX collagen
  • MATN3, which encodes MATN3
  • DTDST or SLC26A2, which encodes the diastrophic dysplasia sulfate transporter (DTDST or SLC26A2)

Most autosomal dominant forms of MED are attributed to a COMP mutation. [14] COMP is located on chromosome 19. Only a few cases of autosomal dominant MED are characterized by mutations in MATN3,COL9A1, COL9A2, or COL9A3.

All recessive forms of MED are related to mutations in SLC26A2 and involve the peripheral joints. [14]

Previous
Next:

Prognosis

Few investigators have described the outcomes of surgical treatment for MED. Lim et al reported on total hip replacement with the use of modular cementless prostheses. [15] At a mean follow-up of 4.8 years, no hip required revision. Harris hip scores seemed to be substantially improved.

Previous