Multiple epiphyseal dysplasia (MED)

COMP related disorders

Pseudoachondroplasia (PSACH; MIM 177170) and some cases of autosomal dominant multiple epiphyseal dysplasia (MED; MIM 132400) are caused by mutations in the COMP gene which codes for cartilage oligomeric matrix protein.

Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous chondrodysplasia with either autosomal dominant or recessive inheritance. The phenotypic spectrum ranges from mild to severe. Patients usually present with joint pain and stiffness, waddling gait and/or mild short stature in childhood. However, some patients remain asymptomatic until adulthood and present with early-onset osteoarthritis of the large weight-bearing joints. Typical radiographic findings include delayed and irregular ossification of the epiphyses in multiple joints.  In some cases mild spinal changes may also be present.  Autosomal dominant MED can be caused by mutations in the COMP (EDM1; MIM 132400), COL9A1, COL9A2 (EDM2; MIM 600204), COL9A3 (EDM3; MIM 600969) or MATN3 genes (EDM5; MIM 607078).  Autosomal recessive MED (EDM4; MIM 226900) can be caused by mutations in the diastrophic dysplasia sulfate transporter gene (DTDST or SLC26A2). The majority of patients with autosomal dominant MED have a mutation in the COMP gene.

Pseudoachondroplasia (PSACH; MIM 177170) is an autosomal dominant disorder caused by mutations in the COMP gene. The disorder becomes evident between one and two years of age when skeletal growth decelerates and a waddling gait develops. Disproportionate short stature, accentuated limb shortening with age, generalized ligamentous laxity and short broad hands are characteristic. Windswept deformities of the knees and bowed forearms also occur. Osteoarthritis of the hips and knees is common.