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.


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


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.


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  7. http://www.omim.org