It is a very rare genetic disorder characterized by irregular epiphyseal growth, skeletal deformities, short-limb dwarfism, pain, and stiffness of affected joints. The main clinical features include a waddling gait, reduced height in adults with limbs relatively short in comparison to the trunk, and normal intelligence. Several types of MED have been described, but two are important to mention. They are a mild form or Ribbing type, and a severe form or Fairbank type. In the mild form, the hands and wrists are usually normal, whereas in the severe form, the hands and feet are short and stubby.
Multiple epiphyseal dysplasia was first described separately by Seved Ribbing and Harold Arthur Thomas Fairbank in the 1930s. In the 1990s, much has been accomplished in the identification of the genetic alliances with the different types. In 1994, Ralph Oehlmann’s group mapped MED to the pericentromeric region of chromosome 19. In 1995, Michael Briggs’ group linked the COMP gene to pseudoachondroplasia (PASCH).
There are several subtypes that have been described. They consist of the following:
MED Type I (Fairbank Epiphyseal Dysplasia; Beighton Goldberg Hoff Syndrome; Ribbing Epiphyseal Dysplasia): Severe osteoarthritis of the hips and changes in the distal tibia develop in early adulthood. A deficiency in the lateral part of the distal tibial ossification center is seen in children. Short stature and brachydactyly are features.
MED Type II: Affected individuals typically presented at age 2.5 to 6 years with pain in the knees. Knee and ankle pain was present throughout childhood. Bilateral osteotomies were required for gross varus deformities of the knees in some individuals. Hands were mildly short and joints prominent. There were no abnormalities of the spine or chest. Examination of radiographs revealed flattened, irregular epiphyses in most joints, particularly the knees. Childhood radiographs showed small epiphyses with a large physeal space. The vertebrae appeared normal in adulthood, but there were some anterior defects at earlier ages.
MED Type III (Multiple Epiphyseal Dysplasia Myopathy Syndrome): Typically present during childhood and adolescence, with waddling gait and stiffness and/or pain in the knees. Few patients experience involvement of other joints, such as the elbow, wrist, or ankle, short stature, and stubby hands. There are no spine abnormalities, and the radiographs show flattened, irregular epiphyses, varus or valgus deformity of the knees, and precocious osteoarthritis of the hips requiring early hip replacement.
MED Type IV (Ribbing type; Autosomal Recessive Multiple Epiphyseal Dysplasia; Multiple Epiphyseal Dysplasia with Clubfoot; Multiple Epiphyseal Dysplasia with Bilayered Patellae): Characterized by bilateral clubfoot and bilateral double-layered patellae.
MED Type V (Multiple Epiphyseal Dysplasia MATN3-related): Characterized by normal birth length and adult height around the third percentile 150 to 165 cm; however, patients complained of knee and hip pain after exercise during early childhood. Radiographs at or after the age ...