There is nothing a parent can do before, during or after a pregnancy to cause osteopetrosis in a child.The genes associated with osteopetrosis are involved in the development and/or function of osteoclasts, cells that break down bone tissue when old bone is being replaced by new bone (bone remodeling). This process is necessary to keep bones strong and healthy. Mutations in these genes can lead to abnormal osteoclasts, or having too few osteoclasts. If this happens, old bone cannot be broken down as new bone is formed, so bones become too dense and prone to breaking. Mutations in the CLCN7 gene cause most cases of autosomal dominant osteopetrosis, 10-15% of cases of autosomal recessive osteopetrosis (the most severe form), and all known cases of intermediate autosomal osteopetrosis. Mutations in the TCIRG1 gene cause about 50% of cases of autosomal recessive osteopetrosis. Mutations in the IKBKG gene cause X-linked osteopetrosis. Mutations in other genes are less common causes of osteopetrosis. In about 30% percent of affected people, the cause is unknown.Normally, bone growth is a balance between osteoblasts (cells that create bone tissue) and osteoclasts (cells that destroy bone tissue). Those with osteopetrosis have a deficiency of osteoclasts, meaning too little bone is being resorbed, resulting in too much bone being created. Gene variation
Mechanisms
Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (breakdown of bone matrix) by osteoclasts. In osteopetrosis, the number of osteoclasts may be reduced, normal, or increased.
Most importantly, osteoclast dysfunction mediates the pathogenesis of this disease.Osteopetrosis is caused by underlying mutations that interfere with the acidification of the osteoclast resorption pit, for example due to a deficiency of the carbonic anhydrase enzyme encoded by the CA2 gene. Carbonic anhydrase is required by osteoclasts for proton production. Without this enzyme hydrogen ion pumping is inhibited and bone resorption by osteoclasts is defective, as an acidic environment is needed to dissociate calcium hydroxyapatite from the bone matrix. As bone resorption fails while bone formation continues, excessive bone is formed.Mutations in at least nine genes cause the various types of osteopetrosis. Mutations in the CLCN7 gene are responsible for about 75 percent of cases of autosomal dominant osteopetrosis, 10 to 15 percent of cases of autosomal recessive osteopetrosis, and all known cases of intermediate autosomal osteopetrosis. TCIRG1 gene mutations cause about 50 percent of cases of autosomal recessive osteopetrosis. Mutations in other genes are less common causes of autosomal dominant and autosomal recessive forms of the disorder. The X-linked type of osteopetrosis, OL-EDA-ID, results from mutations in the IKBKG gene. In about 30 percent of all cases of osteopetrosis, the cause of the condition is unknown.The genes associated with osteopetrosis are involved in the formation, development, and function of specialized cells called osteoclasts. These cells break down bone tissue during bone remodeling, a normal process in which old bone is removed and new bone is created to replace it.