Diagnosis
Diagnosis should be based on the clinical and radiographic findings and a genetic analysis can be assessed. Treatment
Symptomatic individuals should be seen by an orthopedist to assess the possibility of treatment (physiotherapy for muscular strengthening, cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs). Although there is no cure, surgery is sometimes used to relieve symptoms. Surgery may be necessary to treat misalignment of the hip (osteotomy of the pelvis or the collum femoris) and, in some cases, malformation (e.g., genu varum or genu valgum). In some cases, total hip replacement may be necessary. However, surgery is not always necessary or appropriate.Sports involving joint overload are to be avoided, while swimming or cycling are strongly suggested. Cycling has to be avoided in people having ligamentous laxity. Weight control is suggested.The use of crutches, other deambulatory aids or wheelchair is useful to prevent hip pain. Pain in the hand while writing can be avoided using a pen with wide grip. History
Multiple epiphyseal dysplasia was described separately by Seved Ribbing and Harold Arthur Thomas Fairbank in the 1930s.In 1994, Ralph Oehlmanns group mapped MED to the peri-centromeric region of chromosome 19, using genetic linkage analysis. Michael Briggs group mapped PSACH to the same area. COMP gene was firstly linked to MED and PSACH in 1995. In 1995, the group led by Knowlton did a "high-resolution genetic and physical mapping of multiple epiphyseal dysplasia and pseudoachondroplasia mutations at chromosome 19p13.1-p12. "Research on COMP led to mouse models of the pathology of MED.
The following testing regime has been recommended by the European Skeletal Dysplasia Network:
Level 1: COMP (exons 10–15) and MATN3 (exon 2)
Level 2: COMP (exons 8 & 9 and 16–19)
Level 3: COL9A1 (exon 8), COL9A2 and COL9A3 (exon 3)All those genes are involved in the production of the extracellular matrix (ECM). The role of COMP gene remains unclear. It is a noncollagenous protein of the ECM. Mutations in this gene can cause the pseudoachondroplasia (PSACH). It should play a role in the structural integrity of cartilage by its interaction with other extracellular matrix proteins and can be part of the interaction of the chondrocytes with the matrix and it is also a potent suppressor of apoptosis in chondrocytes. Another role is maintaining a vascular smooth muscle cells contractile under physiological or pathological stimuli.Since 2003, the European Skeletal Dysplasia Network has used an online system to diagnose cases referred to the network before mutation analysis to study the mutations causing PSACH or MED.COL9A1, COL9A2, COL9A3 are genes coding for collagen type IX, that is a component of hyaline cartilage. MATN3 protein may play a role in the formation of the extracellular filamentous networks and in the development and homeostasis of cartilage and bone.In the recessive form, the DTDST gene, also known as SLC26A2, is mutated in almost 90% of the patients, causing diastrophic dysplasia. It is a sulfate transporter, transmembrane glycoprotein implicated in several chondrodysplasias. It is important for sulfation of proteoglycans and matrix organization.