Few cases of OI due to mutations in genes coding for proteins that modify or chaperone newly synthesized intracellular type I collagen are described to date. Thus far, most affected individuals have had severe or lethal forms, with marked short stature and multiple fractures. At least six different genes are responsible for these types of OI, all of which are inherited on an autosomal recessive basis.

The diagnosis of any form of OI requires detailed clinical and family histories in addition to a careful physical examination based on knowledge of the common and defining features of OI. Radiologic assessment is essential and should be done by a radiologist knowledgeable in syndromic conditions. Although biochemical assessment of skin fibroblast collagens was the first confirmatory test for OI, it is now possible to sequence COL1A1 and COL1A2 genes as an initial diagnostic tool. Analysis of radiolabeled fibroblast collagens still has diagnostic value in selected clinical contexts.

Management of OI focuses on therapies to minimize fractures and deformities, minimize disability, and promote overall health. Orthopedic management is the mainstay of treatment, along with physical therapy and exercise. In infants, the use of soft bandages is generally adequate for the management of fractures; in children and adolescents, more rigid splints or braces are needed. Significant deformities and recurrent fractures require fixation of the long bones with intramedullary rods. Where significant longitudinal bone growth is anticipated, use of extensible rods is desirable. Physical activity should be encouraged, and immobilization should be kept to a minimum. Scoliosis can be a severe problem in OI, necessitating early and continued attention to the spine. Because braces are usually ineffective, spinal fusion may be needed to avoid severe curvature. Basilar invagination occurs with high frequency in severe OI and when present is usually slowly progressive. It requires surveillance by cranial CT or MRI; surgical intervention, when undertaken, should be done at a center experienced in the procedures used. Proper positioning on the operating room table is an important consideration when general anesthesia is needed.

Hearing loss, when present, is usually a relatively late onset complication and is of a conductive nature, although there is sometimes also a sensorineural basis. Hearing aids can be helpful and, when inadequate, stapedectomy can be a useful option. Cochlear implantation can be helpful for some individuals with significant sensorineural hearing loss. Dentinogenesis imperfecta may require restorative coverage; other dental abnormalities may include malocclusion and abnormalities of tooth eruption. Dental treatment should be done by dentists with expertise in dentinogenesis imperfecta.

Pharmacologic therapy for OI is evolving. Bisphosphonates are now widely administered to children with OI. Positive effects on bone histology are reported, but it is not yet clear if there is a decrease of long bone fractures and there are few data thus far indicating improved strength, motor function, or decreased pain. Treatment with recombinant growth hormone can produce significant increases in linear growth and may also result in improvement of bone histology and vertebral DXA. There is ongoing research regarding many other therapies.

The psychosocial dimensions of living with a multiple-handicapping condition are important. OI support groups can be extremely helpful for affected persons and their families. In addition, genetic counseling regarding reproductive recurrence risk issues and reproductive options should be discussed, if desired. Overall, both the diagnosis and the coordinated care of the child or adult with OI require a multidisciplinary effort by persons with expertise in OI.