Osteogenesis imperfecta 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. Diagnosis is usually clinical. Treatment includes growth hormone for some types and bisphosphonates.
There are 4 main types of osteogenesis imperfecta (OI):
Ninety percent of people who have one of the major types have mutations in the genes encoding the pro-alpha chains of type I procollagen (a structural component of bones, ligaments, and tendons), COL1A1 or COL1A2. Other types are rare and are caused by mutations in different genes.
Hearing loss is present in 50 to 65% of all patients with osteogenesis imperfecta 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 of osteogenesis imperfecta is usually clinical, but there are no standardized criteria.
Analysis of type I procollagen 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 osteogenesis imperfecta can be detected in utero by level II ultrasonography.
Growth hormone helps growth-responsive children (types I and IV).
Treatment with bisphosphonates is aimed at increasing bone density and decreasing bone pain and fracture risk (1). IV pamidronate (0.5 to 3 mg/kg once/day for 3 days, repeated as needed q 4 to 6 mo) or oral alendronate (1 mg/kg, 20 mg maximum, once/day) are used.
Orthopedic surgery, physical therapy, and occupational therapy help prevent fractures and improve function.
Cochlear implantation is indicated in selected cases of hearing loss.