Endosteal Hyperostosis, Autosomal Dominant
A number sign (#) is used with this entry because autosomal dominant endosteal hyperostosis is caused by heterozygous mutation in the LRP5 gene (603506) on chromosome 11q13.
A number of other disorders characterized by increased bone density, e.g., osteoporosis-pseudoglioma syndrome (OPPG; 259770), are caused by mutation in this gene.
Clinical FeaturesMaroteaux et al. (1971) reported a benign and usually asymptomatic form of osteosclerosis associated with torus palatinus. Worth and Wollin (1966) first described the condition.
Gorlin and Glass (1977) proposed the designation for this disorder which is distinguished from van Buchem disease (hyperostosis corticalis generalisata; 239100) by the dominant inheritance pattern and absence of exophthalmos, hypertelorism, increased head circumference, nasal obstruction, cranial nerve involvement, and elevated alkaline phosphatase. A main clinical feature is widened and deepened mandible with increased gonial angle. Radiographically, the disorder shows endosteal sclerosis of the calvaria with loss of the diploe, osteosclerosis and hyperostosis of the mandible with absence of the normal antegonial notches, endosteal sclerosis of the diaphyses of long bones (including metacarpals and metatarsals), and osteosclerosis of the pelvis. The vertebral bodies, ribs, and clavicles are involved to a minor degree. Unlike dominant osteopetrosis (see 166600), osteomyelitis and 'bone-within-bone' x-ray appearance may not occur in this form. Torus palatinus is such a generally common finding--in about 25% of females (Gorlin, 1977)--that it may not be a significant feature. Reports include those of Russell et al. (1968), Dyson (1972), and Owen (1976).
Perez-Vicente et al. (1987) pointed out that the autosomal dominant variety of endosteal hyperostosis may not always be benign. He described a Spanish family in which individuals in 4 generations appear to have been affected. A father and daughter who were studied showed severe involvement. The father showed neurologic damage with sensorineural hearing loss, chronic intracranial hypertension, and mild corticospinal tract abnormalities. There was radiologic evidence of progressive bone disease at follow-up. In addition to mild hydrocephalus, CT scan of the head documented a reduction in size with the posterior fossa and encroachment on the foramen magnum.
Ades et al. (1994) observed this disorder in a mother and her 2 children. Chronic intracranial hypertension and cranial nerve palsies were found in the mother. CT scans and MRI views of the head demonstrated symmetrical sclerosis of the cranial vault, narrow internal auditory meatus and canals, inferior herniation of the cerebellar tonsils into the foramen magnum, and encroachment of occipital bone into the foramen magnum posteriorly.
Molecular GeneticsVan Wesenbeeck et al. (2003) described mutations in the LRP5 gene in several conditions with increased bone density, including heterozygous mutations in affected members of 3 families with endosteal hyperostosis (603506.0015-603506.0016).