Human genetics of SOST.

Van Buchem disease is a rare sclerosing bone dysplasia, first described by van Buchem et al. in 1955. It is also known under the name hyperostosis corticalis generalisata, and is classified among the craniotubular hyperostoses. Radiographic examination shows a generalized, progressive overgrowth and sclerosis of the skeleton. Typical features are an impressive thickening and sclerosis of the mandible and both the roof and base of the skull, often resulting in facial distortion. Facial nerve palsy, hearing disturbances, visual loss and neurological pain, caused by encroachment of the cranial foramina by hyperostotic bone, are frequently observed clinical complications. The clinical phenotype of sclerosteosis is often more severe and variable expression of congenital hand malformations and raised intracranial pressure, sometimes leading to sudden death, is observed. Both conditions are observed with an equal sex distribution, and the prevalence is very low. Only about 40 cases of van Buchem disease and less than 100 sclerosteosis patients have been reported. The prevalence of sclerosteosis has been estimated at 1 in 75,000 in the South African population, where the incidence is the highest, and at least 1 in every 140 Afrikaners is a carrier of the disease-causing mutation.