Autosomal Dominant

Osteosclerosis 1

Opinion

Robert J. Gorlin, M.S., D.D.S., and Lillian Glass, B.S., M.S. Autosomal dominant osteosclerosis, an entity previously labelled by various names, is clearly separate from Van Buchem disease; Van Buchem disease exhibits autosomal recessive inheritance. The clinical manifestation of autosomal dominant osteosclerosis is a widened and deepened mandible with increased gonial angle. Radiographic manifestations include endosteal sclerosis of the neurocranium 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. INDEX TERMS: Bones, osteochondrodysplasias, 4 [8] 151 • Bones, sclerosis, 2[4] 133 • Familial conditions. Hyperostosis. Opinions

Radiology 125:,547-548, November 1977

We would like to make a few apposite observations concerning an entity that has often been mislabelled by a variety of names. The term autosomal dominant osteosclerosis is our choice. It is hardly an ideal or even original label, but it clearly separates the disorder from Van Buchem disease (hyperostosis corticalis generalisata), which exhibits autosomal recessive inheritance. It is axiomatic that one is not dealing with a single disease when a dis-

order exhibits several genetic patterns. In other words, when two disorders appear inseparable (based on clinical and radiographic evidence) they do not exhibit variable genetic transmission, but are different diseases if they differ in inheritance pattern. This should be especially evident when one "variant" has dominant inheritance which involves a structural gene while the other exhibits recessive inheritance, implying a defective or missing

Worth and Wollin (1966)

Russell at al. (1968)

Mlrotelux et II. (1971)

Fig. 1.

Dyson (1972) - Owen (1978)

Pedigrees of examples of autosomal dominant osteosclerosis.

1 From the Division of Oral Pathology, School of Dentistry, University of Minnesota, Minneapolis. Accepted for publication in May 1977. Two related papers appear in this issue on pages 289 and 297. emt

547

548

ROBERT

J.

GORLIN AND LILLIAN GLASS

enzyme. This is termed genetic heterogeneity; it has caused considerable confusion in limning craniotubular disorders. The clinical manifestation of autosomal dominant osteosclerosis is a widened and deepened mandible with increased gonial angle. Radiographically, one notes endosteal sclerosis of the neurocranium 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. There is no exophthalmos, hypertelorism, increased head circumference, nasal obstruction, neurological complications (facial paralysis, optic atrophy, deafness) or elevated serum alkaline phosphatase; together with the dominant inheritance pattern these clearly separate this disorder from autosomal recessive Van Buchem disease. Examples of autosomal dominant osteosclerosis (Fig. 1) are those of Worth and Wollin (1966), Russell et al: (1968), Maroteaux etal. (1971), Dyson (1972), and Owen (1976). For reasons that are not clear, Russell et al. considered the disorder to have X-linked dominant inheritance.

November 1977

Transmission of the disorder from an affected male to all of his daughters and none of his sons is requisite for this mode. There is male-ta-male transmission in the Worth and Wollin kindred if we assume that the cases cited above represent a single entity, which would exclude X-linked inheritance. Robert J. Gorlin, D.D.S., M.S. Division of Oral Pathology School of Dentistry University of Minnesota 515 Delaware St. SE Minneapolis, Minnesota 55455

REFERENCES 1. Worth HM, Wollin DG: Hyperostosis corticalis generalisata congenita. J Can Assoc RadioI17:67-74, Jun 1966 2. Russell WJ, Bizzozero OJ Jr, Omori Y: Idiopathic osteosclerosis. A report of six related cases. Radiology 90:70-76, Jan 1968 3. MaroteauxP, Fontaine G, Scharfman W, et al: L'hyperostose corticale glmeralisee a transmission dominante. Arch Fr Pediatr 28:685-698, Aug-Sep 1971 4. Dyson DP: Van Buchem's disease (hyperostosis cortical is generalista familiaris). A case report. Br J Oral Surg 9:237-245, Mar 1972 5. Owen RJ: Van Buchem's disease (hyperostosis cortical is generalisata). Br J Radiol 49:126-132, 1976