Multiple Epiphyseal Dysplasia

Epiphysis refers to the ends of long bones that are adjacent to the joints. Therefore, this disorder is one that involves more than one epiphysis. MED occurs in approximately 9 in 100,000 live births (4). Initially, two types of MED were identified: Fairbank Type (severe) and Ribbing Type (mild). However, the MED is now considered one clinically heterogenous disorder, and the two classifications have been abandoned (5).

 
How Multiple Epiphyseal Dysplasia Is Inherited

MED is typically inherited in an autosomal dominant manner (2). However, an autosomal recessive form of MED has also been idenitified (2). Due to non-allelic mutations, genetic heterogeneity does occur, resulting in a wide variability of expression.

 
Causes of Multiple Epiphyseal Dysplasia

The Fairbank type of MED is caused by a mutation in the gene encoding the cartilage oligomeric matrix protein, or COMP. A less severe form can be caused by point mutations in any three of the type IX collagen genes (COL9A1, COL9A2, COL9A3). Type IX collagen is found on the surface of type II collagen and is necessary for the integrity of articular cartilage. Another mutation in the gene that encodes matrilin-3 causes a distinctively mild form of MED. Finally, the autosomal recessive form of MED is caused by mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene or by mutations in the solute carrier family 26, member 2 gene (SLC26A2). Overall, the mutations result in a retarded formation of epiphyseal ossification centers. The bones most commonly affected are the humeral and femoral heads. Bones of the pelvis, spinal column and skull are typically normal.

 
Physical Characteristics

MED is a disorder of bone and cartilage development that results in small irregular epiphyses, proportionate short stature, frequently painful joints, and early onset degenerative arthritis. MED is not typically recognized until after two-years of age and in some cases, not until early adulthood. Typically adults will grow to be between 145 and 170 cm.

Face & Skull
  • Normal facial features
Trunk, Chest, & Spine:
  • Accentuated thoracic kyphosis
  • Possibility for blunted, flattened, or slightly ovoid vertebral bodies
Arms & Legs:
What are the X-ray characteristics?

The major radiographic features of MED include irregular epiphyses and, in childhood, irregularity of the tubular bones, usually at the hips, knees, ankles, wrists and hands. In middle to late childhood, the epiphyses are either flat or small. An important sign is the epiphyses of distal tibias are laterally malformed to produce a sloping wedge-shaped articular surface in adults. Bipartite (split) patella is common. Metaphyses are normal with mild shortening of the tubular bones. The phalanges are short and stubby, and the metacarpals have epiphyseal irregularities. Vertebral bodies are flat, with irregular end plates markedly in the thoracic spine.

 
Making the Diagnosis

Clinical features and X-rays are the mainstay of diagnosis.

Mutations in 5 known gene locations account for 50% of cases. Molecular genetic testing is available on a clinical basis for the COMP gene on chromosome 19. Prenatal diagnosis is possible for the COMP mutation, if the diagnosis is suspected on ultrasound.

Often, MED is misdiagnosed as Legg-Calvé-Perthes disease. In order to distinguish between the two conditions, bone scans and full skeletal radiographic surveys are often necessary.

 
Musculoskeletal Problems
Joints

Degenerative joint disease occurs principally in the weight-bearing joints (hips, knees, and ankles) of the lower limbs but is also seen in the shoulders. The joint deformities oftentimes cause progressive “degenerative” osteoarthroses. If gone untreated, patients may be unable to stand or walk by age 50. Around the ages of 30 to 35, joint replacement is sometimes required.

Lower Limbs

Genu varus or valgus oftentimes occur.

 
Problems Elsewhere in the Body

Apart from problems in joints, no other system is affected.

 
What to Look For

Increasing pain, decreased endurance or limping in an individual with MED may be indicative of progressive arthritis. Arthritis develops in MED due to an intrinsic abnormality in the joint cartilage as previously explained. The only solution in the longer term is a hip or shoulder joint replacement. The ankle joint may be involved in MED. Because of the early onset of degenerative arthritis, vigorous, non-weight bearing exercise must be avoided to prevent disability that would require joint replacements. Both swimming and bike riding are recommended. Generally all skeletal dysplasias warrant multidisciplinary attention.

Regular assessment by an orthopedist, geneticist, pediatrician, dentist, neurologist, and physical therapist will provide the most comprehensive treatment.

 
References
  1. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  2. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):17-18.
  3. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
  4. Taybi, H. Lachman, RS. Skeletal Dysplasias. In "Radiology of Syndromes, Metabolic Disorders, and Skeletal Dysplasias." St. Louis: Mosby-Year Book, Inc., pp 858-870. 1996.
  5. Unger, Sheila. Hecht, Jacqueline T. Pseudoachondroplasia and Multiple Epiphyseal Dysplasia: New Etiologic Developments. American Journal of Medical Genetics, 2001; 106: 244-250.

Trusted Insights from Nemours' KidsHealth