Epiphyseal Dysplasia, Multiple, With Myopia And Conductive Deafness

A number sign (#) is used with this entry because of evidence that multiple epiphyseal dysplasia with myopia and conductive deafness (EDMMD) is caused by heterozygous mutation in the COL2A1 gene (120140) on chromosome 12q13.

Clinical Features

Beighton et al. (1978) described an Afrikaner kindred in South Africa in which the mother, her 2 sons, and her daughter had a syndrome of multiple epiphyseal dysplasia, myopia, and conductive deafness. The patients had short stature, brachydactyly, and genu valgus deformity. Radiographic studies of the 10-year-old boy revealed generalized dysplasia of the epiphyses. The epiphyses around the knee joint were flattened and the femoral necks were widened, with a coxa valga deformity. The vertebral bodies were mildly reduced in height and were concave on their upper and lower surfaces. All patients had early-onset progressive myopia, retinal thinning, asteroid hyalosis, and crenated cataracts. See 184000, 226950, and 609324 for syndromes with an overlapping constellation of features. Spondyloepiphyseal dysplasia congenita (183900) also shares many of the same features.

Molecular Genetics

Ballo et al. (1998) performed molecular genetic analysis on the family described by Beighton et al. (1978) and discovered a heterozygous arg-to-cys substitution at residue 704 of the COL2A1 gene, occurring at the X position of the Gly-X-Y motif (120140.0029). This family manifests a dominant-negative mutation, with ocular problems and conductive deafness consistent with Stickler syndrome, but with a radiologic picture of mild multiple epiphyseal dysplasia.