Autosomal dominant osteopetrosis.

Abstract

Autosomal dominant osteopetrosis (ADO) is the most common form of osteopetrosis. ADO is characterized by generalized osteosclerosis along with characteristic radiographic features such as a "bone-in-bone" appearance of long bones and sclerosis of the superior and inferior vertebral body endplates. Generalized osteosclerosis in ADO typically results from abnormalities in osteoclast function, due most commonly to mutations in the chloride channel 7 (CLCN7) gene. A variety of debilitating complications can occur over time due to bone fragility, impingement of cranial nerves, encroachment of osteopetrotic bone in the marrow space, and poor bone vascularity. There is a wide spectrum of disease phenotype, even within the same family. Currently, there is no disease specific treatment for ADO, so clinical care focuses on monitoring for disease complications and symptomatic treatment. This review describes the history of ADO, the wide disease phenotype, and potential new therapies.