Osteopetrosis, Autosomal dominant 2 (OPTA2)/Albers-Schonberg disease

(OMIM phenotype number #166600)

Osteopetrosis is a heterogeneous group of sclerosing bone dysplasias, marked by the inability of osteoclast to resorb bone due to defects in the osteoclastogenesis or the acidification of the extracellular compartment. The hallmark of osteopetrosis is an increased bone density within the medullary portion of the bone and relative sparing of the cortices. Patients with osteopetrosis have decreased osteoclastic activity, increased bone mass, leading to decreased elasticity of the bone or impaired repair capabilities and, therefore, increased risk of fracture. This bone disorder include both autosomal-dominant and autosomal-recessive subtypes.

The autosomal-dominant adult type, so-called ‘Albers-Schonberg disease’, is a benign form and it is associated with few symptoms. The disease is characterized by increased bone density, secondary to a bone resorption defect caused by abnormal osteoclasts. The onset occurs in adolescence or adulthood with variable penetrance. The severity of the clinical manifestation is quite variable, even in the same familiy. Prevalence has been estimated to be 5/100.000. Orthopaedic treatment can be necessary in case of fractures and arthritis, but, until now, any effective medical treatment exists for osteopetrosis.


OPTA2 is caused by loss of chloride channel 7 activity, as a result of deactivating mutations in one allele of the CLCN7 gene, 16p13.3 (OMIM gene/locus number *602727). This disorder is transmitted in an autosomal dominant manner.


Most patients are asymptomatic, although some may have mild anemia due to narrowed medullary. Phenotypic features include: increased bone density (sclerosis) and generalized high bone mass, fractures (80% of cases, often in any long bones and in the posterior arch of the vertebrae, inducing dylolisthesis), scoliosis, hip osteoarthritis, dental abscesses, osteomyelitis of the mandible, cranial nerve compression of the skull base, and hearing and visual loss. Radiological features include: "sandwich vertebra" appearance (dense bands of sclerosis parallel to the vertebral endplates), bone-within-bone pattern mainly at the iliac wings and at some other epiphysis, alternating sclerotic and lucent bands in the iliac wings and near the ends of the long bones, and increased skull base density.

Main biochemical alterations

Adult/intermediate forms: high CK-BB, high bone ALP.

Infantile/severe forms: low Ca, high PTH, high 1,25(OH)2D, high CK-BB, high AP, anemia.


Fig. (a)

Osteopetrosis, Autosomal dominant 2 (OPTA2)/Albers-Schonberg disease

Fig. (b)

Osteopetrosis, Autosomal dominant 2 (OPTA2)/Albers-Schonberg disease

Fig. Radiographies show “sandwich vertebrae” and “bone within a bone” appearance (a: lower thoracic spine frontal view; b: lumbar spine lateral view).

Reproduced from Kirkland JD, O'Brien WT, Osteopetrosis - Classic Imaging Findings in the Spine. J Clin Diagn Res 2015;9:TJ01-2. 

Other resource

Osteopetrosis Society (OPETS)


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