Van Wesenbeeck et al. (2003) described a 724G-A transition in exon 4 of the LRP5 gene, resulting in an ala242-to-thr (A242T) mutation, in 2 previously described families (kindreds A and B) from Portland, Oregon (Beals, 1976; Beals et al., 2001) in which members were affected with autosomal dominant endosteal hyperostosis (144750). The condition is characterized by cortical thickening of the long bones, with no alteration in external shape, and a remarkable resistance of the bone to fracture. The skeleton was normal in childhood; the affected patients had a normal height, proportion, intelligence, and longevity. Facial metamorphoses occurred in adolescence, as the forehead flattened, the mandible became elongated, and the gonial angle decreased. Torus palatinus developed in the hard palate, which could lead to malocclusion or loss of teeth. The clinical and radiographic features closely resembled those of the kindred described by Boyden et al. (2002), in whom a gly171-to-val mutation (G171V; 603506.0013) was identified. The A242T mutation was also present in a previously described Sardinian family (kindred D; Scopelliti et al., 1999) in which at least 5 members had osteosclerosis of the skull and enlarged mandible. The mutation was also present in a French family in which an affected proband and his brother had autosomal dominant osteopetrosis type I (OPTA1; 607634), osteomyelitis of the jaw, and hearing problems because of small auditory canals. X-rays showed diffuse osteosclerosis of the trabecular and cortical bone and osteosclerosis of the skull with enlargement of the cranial vault.
