Oto-spondylo-megaepiphyseal dysplasia (OSMED): Clinical description of three patients homozygous for a missense mutation in the COL11A2 gene

We describe a syndrome of midface hypoplasia, non-progressive sensorineural deafness and epiphyseal dysplasia in 3 sibs born to consanguineous parents. Clinical and roentgenographic findings are compatible with a diagnosis of oto-spondylo-megaepiphyseal dysplasia (OSMED). Histologic study of cartilage shows severe osteoarthritis, which may necessitate joint replacements in early adulthood. Ultrastructurally, collagen fibrils are increased in diameter and show aggregation. These findings have not been reported previously and may be diagnostic of OSMED. The affected sibs are homozygous for a COL11A2 missense mutation. We compare the clinical findings in our patients with a group of patients who have a dominantly inherited, non-ocular form of Stickler syndrome due to a COL11A2 splice-site mutation. Both syndromes include mid-face hypoplasia, epiphyseal dysplasia, and deafness, more pronounced in OSMED. Since mutations affecting the collagen XI genes can obviously result in a spectrum of phenotypes, we performed a literature-search using POSSUM, OSSUM, and the LDDB to identify conditions that might also be caused by mutations in one of the collagen XI genes. A number of conditions matched the search terms in all databases. Of these, Marshall syndrome is very similar to OSMED. Considering these phenotypic similarities and the close association between the COL11A1 and COL11A2 gene products, we propose that Marshall syndrome may be caused by a mutation in COL11A1. We also identify a number of other conditions that could be caused by mutations in one of the collagen XI genes. Am. J. Med. Genet. 70:315–323, 1997. © 1997 Wiley-Liss, Inc.