Autosomal Dominant Osteopetrosis Type 1

A rare sclerosing bone disorder characterized by skeletal densification that predominantly involves the cranial vault.

Epidemiology

It is extremely rare, as only 33 cases have been reported in 3 families.

Clinical description

The disease typically has onset in late childhood or adolescence. Clinical signs include chronic bone pain and disorders of the cranial nerves (trigeminal neuralgia, facial palsy, hearing loss). The risk of fracture is not increased and patients show normal or even increased trabecular bone strength. Twenty to forty percent of cases are asymptomatic.

Etiology

The disease is due to a gain-of-function mutation in the LRP5 gene (Low density lipoprotein receptor-related protein 5; 11q12-q13) which results in increased bone formation. Therefore, controversy exists whether Autosomal dominant osteopetrosis type 1 is truly a type of osteopetrosis (which is due to failure of osteoclast development or function) or whether it is more accurately described as a `high bone mass' disease.

Diagnostic methods

Diagnosis is based on clinical and radiographic evaluation. Radiographs show diffuse skeletal sclerosis, with marked thickening of the cranial vault, slight sclerosis of the spine with dense vertebral arches, and thickened long bone cortices. Bone mineral density (lumbar spine, femoral neck) has a Z-score ranging from +4 to +8 SD.

Genetic counseling

Transmission is autosomal dominant. Each child of an affected individual has a 50% risk of being affected. Autosomal dominant osteopetrosis type 1 is a fully penetrant disease.

Management and treatment

Treatment is symptomatic.

Prognosis

Life expectancy is normal.