Overall, OI occurs with a prevalence of approximately 1 in 15,000 to 20,000 births. Cases due to mutations of the CO1A1 or COL1A2 genes occur in an autosomal dominant manner; more than 1,500 mutations of COL1A1 and COL1A2 are described that cause an abnormality of the quantity or structure of type I collagen. In contrast, OI that is caused by absent or defective function of a type I collagen modifying or chaperone protein occurs on an autosomal recessive basis. In view of the heterogeneity of genetic causes of OI and the diversity of mutations of those loci, it is not unexpected, therefore, that there is marked phenotypic heterogeneity of the various forms of OI. Clinical features that are common to all forms of OI include low bone mass, decreased bone strength, and increased bone fragility.

Historically, an influential early classification of the OIs was developed in the 1970s by Silence and colleagues. Current classifications include the Silence types I to IV, updated by current molecular understanding, as well as additional types that are defined on the basis of the underlying defect of the collagen modifying or chaperone gene or by histology. Type I OI comprises about 50% of cases, is due to null mutations of COL1A1 that are autosomal dominant, and is characterized by normal stature, blue sclerae, and a propensity for fractures (see Plate 3-37). Fractures commonly occur once an affected individual begins to walk (and falls); the frequency of fractures decreases after puberty and then increases again in the fifth decade of life. The number of fractures experienced varies considerably, and fractures usually heal without deformity after appropriate management. Some persons have joint hypermobility that may progress to osteoarthritis. Other physical findings include progressive hearing deficit in about 50% of adults with OI type I. Dentinogenesis imperfecta is uncommon in this form of OI.

OI type II is the perinatal lethal form of OI, although some fetuses die in utero. Affected infants are short and underweight for gestational age and have short and bowed or deformed long bones that have sustained fractures in utero. The calvaria of an affected child is relatively large and undermineralized with a very large anterior fontanel and the sclerae are blue or gray. Most affected infants die in the first week of life, usually from pulmonary insufficiency or pneumonia related to a small thorax and rib fractures. The skeletal abnormalities of OI type II are evident by prenatal ultrasonography. Autosomal dominant mutations of either COL1A1 or COL1A2 cause OI type II. Because of the lethal nature of this type of OI, most affected neonates have de novo mutations, although germline mosaicism has been reported.

OI type III, often termed the progressive deforming type of OI, is the most severe nonlethal form of OI; survival into adulthood can occur with this form. Affected individuals often have fractures at birth and may experience hundreds of fractures during life, even in the absence of apparent trauma. Physical findings include markedly short stature with vertebral compressions and scoliosis. Most affected individuals are nonambulatory. Individuals with OI type III often have triangular facies, frontal bossing, blue or gray sclerae, and dentinogenesis imperfecta; hearing loss is also common and usually begins in the teenage years. Many have platybasia or basilar invagination, which is usually asymptomatic; when symptomatic, it can cause brainstem compression, obstructive hydrocephalus, or syringomyelia. Intellectual function is normal unless there has been cerebral hemorrhage that resulted in cognitive dysfunction. Life expectancy may be reduced due to severe kyphoscoliosis and abnormal chest shape that, in turn, causes restrictive lung disease and right-sided heart failure. Radiologic findings include the presence of multiple fractures, long bone deformities, thin ribs, and osteopenia.