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, bisphosphonates, and denosumab.
There are 4 main types of osteogenesis imperfecta (1):
I: Mild, blue sclerae
II: Neonatal lethal, blue sclerae
III: Progressive, variable scleral hue
IV: Variable and deforming, normal scleral hue
Their mode of inheritance is usually autosomal dominant. Ninety percent of people who have one of these main 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.
There are a number of other, rarer types (types V to XXI), which are caused by mutations in different genes.
Reference
1. Van Dijk FS, Sillence DO: Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A 164A(6):1470–1481, 2014. doi: 10.1002/ajmg.a.36545. Clarification and additional information. Am J Med Genet A 167A(5):1178, 2015. doi: 10.1002/ajmg.a.36784
Symptoms and Signs of Osteogenesis Imperfecta
Hearing loss is present in 50 to 65% of all patients with osteogenesis imperfecta and may occur in any of the 4 main 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 osteogenesis imperfecta 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 progressive and the most severe nonlethal form of osteogenesis imperfecta. 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. This type is variable and deforming. 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
Clinical evaluation
Sometimes analysis of type I procollagen or genetic testing
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.
Treatment of Osteogenesis Imperfecta
Growth hormone
Bisphosphonates
Sometimes denosumab
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
2).
Orthopedic surgery, physical therapy, and occupational therapy help prevent fractures and improve function.
Cochlear implantation is indicated in selected cases of hearing loss.
Treatment references
1. Dwan K, Phillipi CA, Steiner RD, Basel D: Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev CD005088, 2016. doi: 10.1002/14651858.CD005088.pub4
2. Li G, Jin Y, Levine MAH, et alActa Paediatr 107(3):534–537, 2018. doi: 10.1111/apa.14154
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Osteogenesis Imperfecta (OI) Foundation: An organization providing support, education, and research information about OI
