Van Buchem disease type 2, autosomal dominant (VBCH2)

(OMIM #607636)

Van Buchem disease type 2, autosomal dominant, is sclerosing bone dysplasia, that  can be caused by mutation in the Low-Density Lipoprotein Receptor-Related Protein-5 (LRP5) gene (see also VBD).

Gene

LRP5 gene, 11q13.2 (OMIM gene/locus number *603506)

Phenotype

Increased bone density, mostly asymptomatic, associated with osteosclerosis of the skull, increased calvarial thickness, enlarged and squared jaw (decreased gonial angle), enlarged mandible, cranial nerve compression, sensorineural hearing loss (otopharyngeal exostosis), and thickened cortices of long bones.

References
  1. Van Wesenbeeck L, Cleiren E, Gram J, et al. Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet. 2003 Mar;72(3):763-71. Epub 2003 Feb 10.
  2. de Vernejoul MC. Sclerosing bone disorders. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):71-83.
  3. de Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  4. Ihde LL, Forrester DM, Gottsegen CJ, et al. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics. 2011 Nov-Dec;31(7):1865-82.
  5. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  6. http://www.omim.org