Osteopetrosis, Autosomal recessive 4 (OPTB4)

(OMIM phenotype number #611490)

Osteopetrosis, Autosomal recessive 4, is a form of autosomal recessive osteopetrosis (see OPTB1) caused by homozygous or compound heterozygous mutation in the Chloride Channel 7 (CLCN7 gene). CLCN7-dependent OPTB4 is diagnosed at birth or early in infancy due to generalized osteosclerosis and severe haematological deficits. Other clinical manifestations include primary neurological defects, such as cerebral and retinal atrophy. This disease is frequently lethal in early life, despite haematological reconstitution by haematopoietic stem cell transplantation.


CLCN7 gene, 16p13.3 (OMIM gene/locus number #602727), encoding chloride channel 7 responsible for Cl-transport. It is expressed in different cell types in vesicles of the endocytotic-lysosomal pathway. In osteoclasts, ClC-7 is localized also in the ruffled border and is involved in the acidification of the resorption lacuna.


Severe form, increased bone density (sclerosis) and generalized high bone mass, loss of trabecular structure, poor/no definition between cortical and medullary bone, fractures, hepatosplenomegaly, mild optic nerve atrophy, cerebral and retinal atrophy.

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.

Other resource

Osteopetrosis Society (OPETS)


  1. Frattini A, Pangrazio A, Susani L, et al. Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res. 2003 Oct;18(10):1740-7.
  2. De Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  3. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  4. http://www.omim.org