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.
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 age 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 with Myopathy): 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
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 of puberty showed a normal spine
but persisting epiphyseal dysplasia of the hips and knees.
The estimated incidence for MED is believed to be
about 10-15:1,000,000 population.
Autosomal dominant with variable expression.
Chromosomes 1p32 coding for gene COL9A2 and 19p13.1 coding for gene COMP
seem to be linked to this disorder. Mutations are also indicated and account for 35% of affected individuals.
A mutation of the COMP gene on chromosome 19. Fifteen percent have mutations
in other undetermined genes. However, in 50%, a mutation cannot be