Summary
Osteogenesis imperfecta (OI) is a genetic disorder of increased bone fragility and low bone mass. The prevalence is estimated between 1/10,000 and 1/20,000. Age at diagnosis depends on the severity of the disease. The four types of OI described by Sillence (I, II, III and IV) have been completed with three types described by Glorieux (V, VI and VII). The clinically most 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 characterized by non deforming, normal height or mild short stature, blue sclera, and no dentinogenesis imperfecta (DI). Patients with type II present multiple rib and long-bone fractures at birth, marked deformities, broad long bones, low density on skull bones X-rays, and dark sclera. Main signs of the type III include very short stature, 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 radial head, mineralized interosseous membrane, hyperplastic callus, white sclera, and no DI. Main signs of the type VI include moderately short stature, scoliosis, accumulation of osteoid in bone tissue, 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. OI is caused (95%) 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) mutation and CRTAP (3p22) defect correspond to the 3% and 2% of recessive forms of OI, respectively. The diagnosis is based on clinical skeletal and extra skeletal findings. Radiological studies reveal osteoporosis and the presence of wormian-like bones. Bone densitometry confirms low bone mass. Differential diagnoses include in utero diagnosis of chondrodysplasia, idiopathic juvenile osteoporosis, osteoporosis pseudoglioma syndrome, Cole-Carpenter and Bruck syndromes, hyper or hypo phosphatasia, panostotic fibrous dysplasia (see these terms), non-accidental injury (many fractures without osteoporosis), and osteoporosis due to a treatment, a deficiency, a metabolic disease, or a leukemia. Furthermore, the several fractures should not lead to diagnosis of Silverman syndrome. Antenatal diagnosis may be performed using ultrasonography or through molecular analysis of amniocytes or chorionic villus cells if the causative mutation was found in the family. The management of OI includes multidisciplinary approach with experienced medical, orthopedic, physiotherapy and rehabilitation specialists. Bisphosphonates with potent anti-resorptive properties are now considered 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). The early physical therapy guides the motor inability and reduces the falls in order to optimize autonomy then to choose a sport activity throughout life. Functional prognosis depends on the severity of the disease and on the quality of management. Vital prognosis depends on respiratory complications correlated with spinal deformities. *Author: Dr. V. Forin (May 2009)*.
