Spondyloepimetaphyseal dysplasia: clinical and radiologic investigation of a large kindred manifesting autosomal dominant inheritance, and a review of the literature.

Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of skeletal disorders that can have a genetic basis, but their classification and prognostication suffer because few families have been extensively studied. We describe a large kindred affected by a unique type of SEMD that is transmitted as an autosomal dominant trait. The propositus and his affected brother and first cousin were evaluated as inpatients. Other kindred members were screened by telephone interviews and lateral thoraco-lumbar spine radiographs, and then, in most cases, investigated by additional x-ray studies. Of the 29 living members of the kindred, 22 were studied radiologically. Among the 22 subjects investigated, 15 were affected, and the status of 1 individual with minor changes on x-ray was indeterminate. The deceased patriarch was presumed to be affected. These 16 affected subjects could usually, but not invariably, be distinguished from their unaffected sex-matched siblings by their smaller heights. Nevertheless, it was only affected children who had short stature; the heights of all affected adults were normal. Often, affected individuals had rhizomelic shortening, especially of the lower extremities, and genu varum (not always evident clinically, but present on radiographs). Occasionally, they also manifested limited extension of their upper limbs. Radiologic study showed abnormal metaphyses, epiphyses, and vertebrae in affected children, but these 3 skeletal regions became less remarkable by late childhood and most affected adults had normal epiphyses. One obligate affected man had only spinal changes. Despite their normal heights, severely affected adults who had bowing deformity of their legs developed disabling degenerative joint disease limited to the knees in the 7th decade of life--disease severe enough to require knee replacement surgery.