Dysplasia epiphysealis hemimelica (DEH) and
metachondromatosis (MC) are considered in the differential diagnosis of solitary and hereditary
osteochondromas. Both are rare disorders with DEH demonstrating cartilaginous overgrowth of an epiphysis and MC exhibiting synchronous
enchondromas and
osteochondromas. Ten cases of DEH and two of MC were compared with
osteochondromas at the histological and molecular level. Histologically, clumping of chondrocytes within a fibrillary chondroid matrix is characteristic of DEH, while
osteochondromas and MC display the characteristic growth plate architecture. Using
cDNA microarray analysis we demonstrate that DEH and MC cluster separately from
osteochondromas and growth plates. The EXT genes, involved in the hereditary
multiple osteochondromas syndrome, and downregulated in
osteochondroma, were normally expressed in DEH and MC as shown by quantitative
reverse transcriptase-polymerase chain reaction (qPCR). EXT is involved in heparan sulphate biosynthesis, important for Indian Hedgehog/
ParaThyroid Hormone Like
Hormone (IHH/PTHLH) growth plate signalling pathways. IHH/PTHLH signalling molecules were expressed in DEH and MC as shown by both qPCR and immunohistochemistry, suggesting that this pathway is active. This is in contrast to
osteochondroma, in which PTHLH signalling is downregulated. Thus, lesions of DEH and MC are separate entities from
osteochondroma as confirmed by their different
cDNA and
protein expression profiles. Downstream targets of EXT, which are downregulated in
osteochondroma, are expressed in DEH and MC, suggesting that EXT signalling is not disturbed.