Van Buchem Disease (Hyperostosis Corticalis Generalisata) Maps to Chromosome 17q12-q21

Abstract

Van Buchem disease (hyperostosis corticalis generalisata; OMIM 239100 [http://www3.ncbi.nlm.nih. gov:80/htbin-post/Omim/dispmim?239100]) is an autosomal recessive disorder characterized by hyperostosis of the skull, mandible, clavicles, ribs, and diaphyseal cortices of the long bones. The most striking clinical features are the enlargement of the jaw and the thickness of the skull, which may lead to facial nerve palsy, hearing loss, and optic atrophy. Increased formation, by osteoblasts, of qualitatively normal bone has been proposed as the underlying pathological mechanism, but the molecular defect is unknown. We studied 11 van Buchem patients and their highly inbred family, who live in The Netherlands in a small ethnic isolate, that had a common ancestor approximately 9 generations ago. A genomewide search with highly polymorphic microsatellite markers showed linkage to marker D17S1299 on chromosome 17q12-21 (maximum LOD score of 8.82 at a recombination fraction [straight theta] of .01). Analysis of additional markers from that region delineated a candidate region of <1 cM, between markers D17S1787 and D17S934. Interestingly, the only marker not showing recombination with the disease locus was an intragenic marker of the thyroid-hormone receptor alpha1 (THRA1) gene, which generated a LOD score of 12.84 at straight theta=.00. Since thyroid hormones are known to stimulate bone resorption, the THRA1 gene might be involved in the etiology and pathogenesis of van Buchem disease. Unraveling the underlying mechanism for this disorder could contribute to the understanding of the regulatory processes conditioning bone density and the underlying pathological processes.

Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriers

“…The phenotype of our patients with VBD is in keeping with previously described clinical features of the disease 1–3, 15, 22, 25. Our data also confirm that the clinical course of VBD is less severe than that of sclerosteosis, in which the majority of patients develop conductive hearing loss in early childhood and raised intracranial pressure around adolescence or early adulthood,4, 11 the latter being the main cause of death in patients with sclerosteosis.…”

Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriers

“…The phenotype of our patients with VBD is in keeping with previously described clinical features of the disease 1–3, 15, 22, 25. Our data also confirm that the clinical course of VBD is less severe than that of sclerosteosis, in which the majority of patients develop conductive hearing loss in early childhood and raised intracranial pressure around adolescence or early adulthood,4, 11 the latter being the main cause of death in patients with sclerosteosis.…”

Greater palatine foramen – key to successful hemimaxillary anaesthesia: a morphometric study and report of a rare aberration

“…The entire skull has a roughened surface covered with flat excrescences or exostoses, and the sutures are obliterated due to new bone formation. (20) Keeping in mind the obvious characteristics of such skulls, it was evident that the anomalous skull noted in the present study does not fit into the category of this syndrome. Moreover, apart from the bilateral absence of the GPF, the only other major foramina found to be absent were those for the carotid canals.…”

Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease

“…In 1976, Van Buchem et al 4 described a total of 15 patients of Dutch origin. Eight patients from this study and five additional van Buchem patients described by Van Hul et al 5 in 1998 have been shown to belong to one extended, highly consanguineous family with a common ancestor in the 18th century. Besides these, one family with four affected sibs 6 and a few isolated cases [7][8][9][10][11] have been reported.…”

Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriers

“…The phenotype of our patients with VBD is in keeping with previously described clinical features of the disease 1–3, 15, 22, 25. Our data also confirm that the clinical course of VBD is less severe than that of sclerosteosis, in which the majority of patients develop conductive hearing loss in early childhood and raised intracranial pressure around adolescence or early adulthood,4, 11 the latter being the main cause of death in patients with sclerosteosis.…”

Greater palatine foramen – key to successful hemimaxillary anaesthesia: a morphometric study and report of a rare aberration

“…The entire skull has a roughened surface covered with flat excrescences or exostoses, and the sutures are obliterated due to new bone formation. (20) Keeping in mind the obvious characteristics of such skulls, it was evident that the anomalous skull noted in the present study does not fit into the category of this syndrome. Moreover, apart from the bilateral absence of the GPF, the only other major foramina found to be absent were those for the carotid canals.…”

Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease

“…In 1976, Van Buchem et al 4 described a total of 15 patients of Dutch origin. Eight patients from this study and five additional van Buchem patients described by Van Hul et al 5 in 1998 have been shown to belong to one extended, highly consanguineous family with a common ancestor in the 18th century. Besides these, one family with four affected sibs 6 and a few isolated cases [7][8][9][10][11] have been reported.…”

Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriers

“…The phenotype of our patients with VBD is in keeping with previously described clinical features of the disease 1–3, 15, 22, 25. Our data also confirm that the clinical course of VBD is less severe than that of sclerosteosis, in which the majority of patients develop conductive hearing loss in early childhood and raised intracranial pressure around adolescence or early adulthood,4, 11 the latter being the main cause of death in patients with sclerosteosis.…”

Greater palatine foramen – key to successful hemimaxillary anaesthesia: a morphometric study and report of a rare aberration

“…The entire skull has a roughened surface covered with flat excrescences or exostoses, and the sutures are obliterated due to new bone formation. (20) Keeping in mind the obvious characteristics of such skulls, it was evident that the anomalous skull noted in the present study does not fit into the category of this syndrome. Moreover, apart from the bilateral absence of the GPF, the only other major foramina found to be absent were those for the carotid canals.…”

Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease

“…In 1976, Van Buchem et al 4 described a total of 15 patients of Dutch origin. Eight patients from this study and five additional van Buchem patients described by Van Hul et al 5 in 1998 have been shown to belong to one extended, highly consanguineous family with a common ancestor in the 18th century. Besides these, one family with four affected sibs 6 and a few isolated cases [7][8][9][10][11] have been reported.…”