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Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity. Prevalence is estimated at between 1/10,000 and 1/20,000. Age at diagnosis depends on the severity of the disease. Five clinically distinct types of OI have been identified. The most clinically relevant characteristic of all types of OI is bone fragility, which manifests as multiple spontaneous fractures. Osteogenesis imperfecta type II is lethal, type III is severe, types IV and V are moderate, and type I is mild (see these terms). Type I is nondeforming with normal height or mild short stature, blue sclera, and no dentinogenesis imperfecta (DI; see this term). Patients with type II present multiple rib and long bone fractures at birth, marked deformities, broad long bones, low density on skull X-rays, and dark sclera. The main signs of type III include very short stature, a triangular face, severe scoliosis, grayish sclera, and DI. Patients with type IV have moderately short stature, mild to moderate scoliosis, grayish or white sclera, and DI. Type V is characterized by mild to moderate short stature, dislocation of the radial head, mineralized interosseous membranes, hyperplastic callus, white sclera, and no DI. Other genetically different types have been observed (types VI to IX) but they are not clinically different from types II-IV. In 95% of cases, OI is caused by mutations in the COL1A1 and COL1A2 genes (17q21.33 and 7q21.3) encoding the alpha1 and alpha2 chains of type 1 collagen. These mutations can cause all five clinical types of OI. Transmission is autosomal dominant. Autosomal recessive forms of OI are also observed and are caused by mutations in the LEPRE1, CRTAP, and PPIB genes (1p34.1, 3p22 and 15q21-q22). Autosomal recessive forms are always severe forms with severe hypotonia. Diagnosis is based on skeletal and extra-skeletal clinical findings. Radiological studies reveal osteoporosis and the presence of wormian-like bones. Bone densitometry confirms the low bone mass. Differential diagnoses include in utero diagnosis of chondrodysplasia, idiopathic juvenile osteoporosis, osteoporosis-pseudoglioma syndrome, Cole-Carpenter and Bruck syndromes, hyper or hypophosphatasia, panostotic form of polyostotic fibrous dysplasia (see these terms), non-accidental injury (multiple fractures without osteoporosis), and osteoporosis due to medication, nutritional deficiency, metabolic disease, or leukemia. The presence of several fractures should not lead to the assumption of child abuse. Antenatal diagnosis may be suspected through ultrasonography and/or confirmed through molecular analysis of amniocytes or chorionic villus cells if the causative mutation in the family has been identified. Management should be multidisciplinary involving experienced medical, orthopedic, physiotherapy and rehabilitation specialists. Bisphosphonates with potent antiresorptive properties are now considered as the standard of care for severe forms but do not constitute a cure. Prevention of vitamin D and calcium deficiency is essential throughout life. Surgical management is essential for the correction of bone and spinal deformities and the prevention of long bone fractures (centro-medullary osteosynthesis). Early physiotherapy improves autonomy by helping to evaluate any motor deficits, reducing the risk of falls and encouraging patients to take up a sporting activity. Functional prognosis depends on the severity of the disease and on the quality of management. Vital prognosis depends on the severity of any respiratory complications associated with spinal deformities.
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