Summary
Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility and low bone mass. Prevalence is estimated at between 1/10,000 and 1/20,000. Age at diagnosis depends on the severity of the disease. Four types of OI (I, II, III and IV) were described by Sillence and three additional forms (V, VI and VII) were described by Glorieux. The most clinically relevant characteristic of all types of OI is bone fragility which manifests by multiple spontaneous fractures. Type II is lethal, type III is severe, types IV, V, VI, VII are moderate, and type I is mild. 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. The main signs of type VI include moderately short stature, scoliosis, osteoid accumulation in bone tissue, a fish-scale pattern of bone lamellation, white sclera, and no DI. Patients with type VII have mild short stature, short humeri and femora, coxa vara, white sclera, and no DI. In 95% of cases, OI is caused by mutations in the COL1A1 (17q21.33) and COL1A2 (7q21.3) genes encoding the alpha1 and alpha2 chains of type 1 collagen, respectively. Transmission is autosomal dominant. LEPRE1 (1p34.1) mutations and CRTAP (3p22) defects are implicated in 3% and 2% of cases of the recessive forms of OI, respectively. The 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 a treatment, a deficiency, a metabolic disease, or leukemia. Furthermore, 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 of OI 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 the 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. *Author: Dr. V. Forin (May 2009)*.
