Osteopetrosis 1 (TCIRG1)
Osteopetrosis 1 is an autosomal recessive bone disorder caused by pathogenic variants in the gene TCIRG1. It is particularly prevalent in Costa Rica and certain areas of Russia due to the presence of founder mutations, but it may be identified in individuals of any ethnicity. This disease is characterized by disruption of the normal balance of bone growth and breakdown, resulting in bone overgrowth. Excess bone in the skull can result in a blockage in the back of the nose, causing feeding and respiratory deficiencies. Progressive growth of bone in the skull can also cause blindness and hearing loss. Because bone cannot be broken down in a normal way, calcium deficits may occur and cause seizures. Thicker bones limit the area available for the bone marrow, resulting in bone marrow insufficiency that may be fatal if untreated. Treatment includes surgery, bone marrow transplants and blood transfusions, but childhood mortality is high. No genotype-phenotype correlation is known.
For information about carrier frequency and residual risk, please see the residual risk table.