Osteopetrosis

Two main forms of osteopetrosis have been delineated: a severe autosomal recessive form (OMIM 259700) with an incidence of ∼1/250,000 births and a mild autosomal dominant form (OMIM 166600) with an incidence of ∼1/20,000 births. Disturbances of osteoclast function due to mutations in a gene encoding an osteoclast-specific subunit of the vacuolar proton pump (TCIRG1) are found in most patients with the recessive form. Mutations of the gene encoding the chloride channel protein, CLCN7, are observed in the dominant form of osteopetrosis. Both types of mutations lead to disturbances of acidification needed for normal osteoclast function.

The severe form is usually detected in infancy or earlier because of macrocephaly, hepatosplenomegaly, deafness, blindness, and severe anemia. Radiographs reveal diffuse bone sclerosis. Later films show the characteristic bone-within-bone appearance (Fig. 690-1). With time, infants typically fail to thrive and show psychomotor delay and worsening of cranial neuropathies and anemia. Dental problems, osteomyelitis of the mandible, and pathologic fractures are common. The most severely affected patients die during infancy; less severely affected patients rarely survive beyond the 2nd decade. Those who survive beyond infancy usually have learning disorders but might have normal intelligence despite hearing and vision loss.

Figure 690-1

Buy Membership for Pediatrics Category to continue reading. Learn more here