9) or an elongation of the pars interarticularis of L5, all of which are fostered by bone fragility and/or hyperlordosis. Spondylolysis of L5, with or without consecutive spondylolisthesis, is also common in children with OI due to a fracture (Fig. In the spine, multiple thoracolumbar compression fractures may be seen (Fig. Diaphyseal fractures may be complete (Fig. The most common fractures occur in the long bone diaphyses, the spine and the apophyses.
Some children may have few or no fractures, whereas others experience numerous fractures throughout their lives, especially when they start walking. These fractures are similar to those seen in normal children who suffer trauma and usually consolidate within the normally expected times. They affect both the axial and appendicular skeletons. However, when such causes have been excluded, DEXA may help to establish the diagnosis of OI and to monitor the response to biphosphonates. Decreased bone mineral density is not specific for OI it may be encountered in metabolic disorders (hypogonadism, growth hormone deficiency, hyperthyroidism, juvenile diabetes mellitus, calcium and vitamin D deficiency, etc.). Bone densitometry by dual-energy X-ray absorptiometry (DEXA) is currently the optimal method to detect decreased bone mineral density, but in children, accurate interpretation of the results requires a good knowledge of the potential pitfalls related to age, sex, pubertal stage and skeletal maturation. This finding, however, is subjective and may be difficult to assess with conventional radiography, and its detection requires a significant reduction (about 30 to 50 %) in calcified bone mass. Radiographs reveal cortical bone thinning and excessive trabecular bone transparency (Figs. When termination of pregnancy is performed based on the discovery of ultrasound and CT abnormalities, postmortem radiographs are a very useful adjunct to diagnosis, in confirming and specifying foetal bone abnormalities (Fig. The role of MRI is limited, except when visualisation of the foetal brain or visceral organs is required to look for associated abnormalities or to assess foetal lung volume. In case of doubt and when a termination of pregnancy is being considered, low-dose computed tomography (CT) with three-dimensional reconstructions of the whole foetal skeleton can be performed, after 26 weeks of gestation, to yield a correct diagnosis. Otherwise, examination may show abnormalities of the skull, the rib cage, the spine or the limbs, such as decreased echogenicity due to insufficient mineralisation, deformities related to fractures, callus formation and increased bone plasticity, and micromelia, especially of the femur (Fig. Nonspecific signs such as intra-uterine growth retardation or hydramnios may be seen. Severe forms of OI (mainly type II) can be diagnosed by ultrasound during the second trimester of pregnancy. This classification is not always easy to use, as some patients cannot be included (and some genetic mutations are still to be discovered), and it is usually more convenient in practice to distinguish between cases diagnosed before or at birth (i.e., severe forms of OI) and cases diagnosed after birth (i.e., milder forms of OI). More recently, three types whose phenotype is similar to other types of OI but that are not associated with type I collagen mutations have been added by Glorieux et al. The classification most widely used for OI distinguishes four types, based on clinical findings and disease severity (Table 1).
The hallmarks of OI are therefore bone fragility and other connective-tissue manifestations, with a large variation in phenotype.
Genetic mutations affect the spatial arrangement of the polypeptide chains and consequently alter the biomechanical properties of type I collagen, particularly its resistance to stretching. The latter is a component of many tissues such as bone, dental enamel, eye sclera, skin, tendons and ligaments. These polypeptide chains form a triple helix of intracellular type I procollagen, which is the precursor of extracellular type I collagen. In the vast majority of cases, it results from mutations in either the COL1A1 or the COL1A2 gene, encoding the pro-alpha 1 and pro-alpha 2 chains, respectively. OI is rare but far from exceptional, affecting approximately 1 in 10,000–20,000 births. It is usually characterised by an autosomal dominant mode of inheritance (95 % of cases), but some cases are related to autosomal recessive traits or to a spontaneous mutation. Also known as “brittle bone disease”, osteogenesis imperfecta (OI) is a genetic disorder characterised by increased bone fragility and low bone mass density due to quantitative and/or qualitative abnormalities of type I collagen.