Osteogenesis imperfecta (OI) is a hereditary collagen disorder causing diffuse abnormal fragility of bone and is sometimes accompanied by sensorineural hearing loss, blue sclerae, dentinogenesis imperfecta, and joint hypermobility.
There are 4 main types of OI; types I and IV are autosomal dominant, whereas types II and III are autosomal recessive. Ninety percent of people who have one of the major types have mutations in the genes encoding the pro-alpha chains of procollagen type I, COL1A1 or COL1A2. Other types are rare and are caused by mutations in different genes.
Symptoms and Signs
Hearing loss is present in 50 to 65% of all patients with OI and may occur in any of the 4 types.
Type I is the mildest. Symptoms and signs in some patients are limited to blue sclerae (due to a deficiency in connective tissue allowing the underlying vessels to show through) and musculoskeletal pain due to joint hypermobility. Recurrent fractures in childhood are possible.
Type II (neonatal lethal type or OI congenita) is the most severe and is lethal. Multiple congenital fractures result in shortened extremities. Sclerae are blue. The skull is soft and, when palpated, feels like a bag of bones. Because the skull is soft, trauma during delivery may cause intracranial hemorrhage and stillbirth, or neonates may die suddenly during the first few days or weeks of life.
Type III is the most severe nonlethal form of OI. Patients with type III have short stature, spinal curvature, and multiple, recurrent fractures. Macrocephaly with triangular facies and pectal deformities are common. Scleral hue varies.
Type IV is intermediate in severity. Survival rate is high. Bones fracture easily in childhood before adolescence. Sclera are typically normal in color. Height is moderate-short stature. Accurate diagnosis is important because these patients may benefit from treatment.
Diagnosis is usually clinical, but there are no standardized criteria. Analysis of type I procollagen (a structural component of bones, ligaments, and tendons) from cultured fibroblasts (from a skin biopsy) or sequence analysis of the COL1A1 and COL1A2 genes can be used when clinical diagnosis is unclear. Severe OI can be detected in utero by level II ultrasonography.
Growth hormone helps growth-responsive children (types I and IV). There is limited experience with the use of IV bisphosphonates (eg, pamidronate 0.5 to 3 mg/kg once/day for 3 days, repeated as needed q 4 to 6 mo) with children, but they can increase bone density and decrease bone pain and fracture frequency. Preliminary studies suggest that oral alendronate (1 mg/kg, 20 mg maximum) is also effective. Orthopedic surgery, physical therapy, and occupational therapy help prevent fractures and improve function. Cochlear implantation is indicated in selected cases of hearing loss.
Last full review/revision January 2014 by David D. Sherry, MD; Frank Pessler, MD, PhD
Content last modified January 2014