Osteogenesis imperfecta (IPA: ; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that break easily. : 85  The range of symptoms—on the skeleton as well as on the bodys other organs—may be mild to severe. : 1512  Symptoms found in various types of OI include whites of the eye (sclerae) that are blue instead, short stature, loose joints, hearing loss, breathing problems and problems with the teeth (dentinogenesis imperfecta). Potentially life-threatening complications, all of which become more common in more severe OI, include: tearing (dissection) of the major arteries, such as the aorta;: 333  pulmonary valve insufficiency secondary to distortion of the ribcage;: 335–341  and basilar invagination. : 106–107 The underlying mechanism is usually a problem with connective tissue due to a lack of, or poorly formed, type I collagen. : 1513  In more than 90% of cases, OI occurs due to mutations in the COL1A1 or COL1A2 genes. These mutations may be inherited from a persons parents in an autosomal dominant manner but may also occur spontaneously (de novo). There are four clinically defined types: type I, the least severe; type IV, moderately severe; type III, severe and progressively deforming; and type II, perinatally lethal. As of September 2021, 19 different genes are known to cause the 21 documented genetically defined types of OI, many of which are extremely rare and have only been documented in a few individuals.
Type XIX – OI caused by hemizygous mutation in the MBTPS2 gene on chromosome Xp22.12. Thus far, OI type XIX is the only known type of OI with an X-linked recessive pattern of inheritance, making it the only type that is more common in males than females. OI type XIX disrupts regulated intramembrane proteolysis, which is critical for healthy bone formation. Type XX – OI caused by homozygous mutation in the MESD gene on chromosome 15q25.1. Initial studies of type XX indicate that it may cause global developmental delay, a first among OI types. OI type XX disrupts the Wnt signaling pathway, which is thought to have a role in bone development. Type XXI – OI caused by homozygous mutation in the KDELR2 gene on chromosome 7p22.1. Causes disease clinically similar to types II and III, thought to be related to inability of chaperone protein HP47 to unbind from collagen type I, as to do so it needs to bind to the missing ER lumen protein retaining receptor 2 protein encoded by KDELR2.Given the rapid rate of type discovery, it is extremely likely that there are other genes associated with OI that have yet to be reported. : 491–492

Genetics
Osteogenesis imperfecta is a group of genetic disorders, all of which cause bone fragility.