A new familial sclerosing bone dysplasia

Abstract

Osteoscleroses are a heterogeneous group of bone remodeling disorders characterized by an increase in bone density. Here we report on a consanguineous Lebanese family in which two sisters, aged 39 and 36 years, exhibit a severe genu varum, a square-face appearance, high forehead, slight proptosis of the eyes, symmetric enlargement of the jaw, protruding chin, and short stature. Bone X-rays showed the presence of hyperostosis of the cranial base and vault with increased density of the orbits, hyperostosis of the bones, thickening of the cortices, diaphyseal modeling defects, cortical thickening of the medullary cavity, mild enlargement of the medullary cavity of the short long bones, short femoral necks, increased width of the ribs, and narrow interpedicular distances of the lower lumbar spine. Osteodensitometry showed values 200% to 300% above values for age. A cervical MRI revealed the presence of a diffuse osteosclerosis with calcification of the posterior vertebral ligament and a narrow canal between C2 and T2. Blood test results were unremarkable. Serum osteocalcin levels were in the normal range, whereas high values of serum C-telopeptide were noted. A bone biopsy showed only the presence of compact bone and did not allow for histomorphometric analysis. Molecular studies excluded genes known to be involved in sclerosing bone dysplasias as the cause of this condition. In vitro analysis of osteoclast function indicated that contrary to most cases of autosomal recessive osteopetrosis, osteoclasts both formed and resorbed but exhibited a small decrease in resorptive activity compared with osteoclasts generated from normal control individuals. Differential diagnoses are discussed, and the possibility that this may be a novel clinical entity is raised.