Osteosclerosis/endosteal hyperostosis, autosomal dominant

(OMIM phenotype number #144750)

Osteosclerosis/endosteal hyperostosis, autosomal dominant, is a sclerosing bone disorder characterized by generalized skeletal densification, particularly of the cranial vault and tubular long bones without an increased risk of fracture (see also VBD). The syndrome has been described in less than 10 families and is due to a mutation in the Low-Density Lipoprotein Receptor-Related Protein-5 (LRP5) gene that leads to increased bone formation. The transmission is autosomal dominant. It can be distinguished from sclerostosis and VBD by a more benign clinical presentation, although the radiological characteristics can be overlapping.

Gene

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

Phenotype

Increased bone density without sclerotic bands, mostly asymptomatic associated with osteosclerosis of the skull (cranial vault), enlarged and squared jaw (decreased gonial angle), no increased risk of fractures (fractures are unusual), cranial nerve compression, sensorineural hearing loss (otopharyngeal exostosis), cortical thickening of the long bones, torus palatinus (an osseous prominence of the palatal vault), normal height, flattened forehead (adolescence), malocclusion, tooth loss, elongated mandible, gonial angle decreased, mild rib sclerosis, mild clavicular sclerosis, mild vertebral body sclerosis, metacarpal and metatarsal diaphyseal endosteal sclerosis.

Main biochemical alterations

High ALP.

References

  1. Worth HM, Wollin DG. Hyperostosis corticalis generalisata congenita. J Can Assoc Radiol. 1966 Jun;17(2):67-74.
  2. Adès LC, Morris LL, Burns R, et al. Neurological involvement in Worth type endosteal hyperostosis: report of a family. Am J Med Genet. 1994 May 15;51(1):46-50.
  3. de Vernejoul MC. Sclerosing bone disorders. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):71-83.
  4. de Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  5. 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.
  6. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  7. http://www.omim.org