Autosomal recessive osteopetrosis

Keywords Disease name / synonyms Excluded Diseases Diagnosis criteria /definition Differential diagnosis Incidence Clinical Description Management including treatment Outcome Etiology Genetics Counseling Antenatal Diagnosis Unresolved questions References Abstract Autosomal recessive "malignant" osteopetrosis is a rare congenital disorder of bone resorption (less than 1:200,000 births). It is caused by the failure of osteoclasts to resorb immature bone. This leads to abnormal bone marrow cavity formation and clinically to the signs and symptoms of bone marrow failure. Impaired bone remodeling causes bony narrowing of the cranial nerve foramina, which results in cranial nerve, especially optic nerve, compression. Pathologically there is a persistence of the primary spongiosa characterized by cores of calcified cartilage within bone. Abnormal remodeling of primary, woven bone to lamellar bone results in "brittle" bone that is prone to fracture. Thus fractures, visual impairment, and bone marrow failure are the classical feature of the disease. Osteopetrosis has been reported in most ethnic groups, although, as the disease is very rare, it is more frequently seen in ethnic groups where consanguinity is common. Infantile onset osteopetrosis should also be distinguished from the much milder autosomal dominant adult disease and the carbonic anhydrase II deficiency syndrome, which is associated with renal tubular acidosis and less severe osteopetrosis. The disease is heterogeneous, and while up to 50% of cases are likely to be due to mutations in the ATP6i gene, a number of genetic etiologies are likely.