الفهرس 
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Abstract
Osteogenesis imperfecta (OI) is a genetic disorder of the connective tissue matrix caused by abnormal collagen microfibril assembly, Several clinical subtypes of OI have been described based on the clinical, biochemical, and molecular nature of the disorder (Basel & Steiner, 2016). The clinical manifestations vary considerably, ranging from a severe perinatal lethal form to a mild disorder which only becomes evident in adulthood, Severe and mild forms share the cardinal feature of bone fragility, which is characterized by bone fractures often after little or no trauma, Several findings in OI are common to other disorders of connective tissues; hypermobile joints and a blue sclera, The incorporation of abnormal type 1 collagen in teeth results in brittle opalescent teeth, the hallmark of Dentinogenesis Imperfecta (DI), often seen in OI, Progressive conductive hearing loss in early adulthood is the result of damage to the ossicles in the middle ear, Short stature, and bone deformity are common features of the disorder (Barnes et al., 2010). In our study, we evaluated children (aged from 1 month up to 18 years) who presented with a history of repeated fractures (more than one) with or without a positive family history of fractures or stillbirths throughout multiple steps for final diagnosis over one and half year duration. History and clinical examination were the first steps to evaluate the patient, not only the fractures which had different age of onset with the commonest age before age of one year (45.7 of cases presented at birth and 28.6% of cases onset before age of year) but also other features of connective tissue affection as dental affection (34.35 of cases), hearing loss (10% of cases), bone deformity (100% of cases), and fragile capillaries (10% of cases) that help us to detect genetic causes of bone fragility mainly osteogenesis imperfecta and exclude other secondary causes. Using laboratory studies helps us to exclude secondary causes of bone fragility in our patients especially renal as renal tubular acidosis, nutritional as rickets, and hematological causes as thalassemia and increase our suspicion in the diagnosis of osteogenesis imperfecta. Evaluation of our studied children with DXA scan to evaluate the degree of bone density and bone mass for accurate measurement of bone hypodensity that presents in plain X-ray and follow up the efficacy of medical treatment on bone density through Z score which had mean value (-2.31± 0.65) before the start of medical treatment and improved after a course of at least 4 doses of zoledronic acid to be (-1.38± 0.43) which reflect the efficacy of medical treatment. The Gene sequencing technique was the final step in our study for confirmation of the diagnosis of osteogenesis imperfecta in highly suspicious cases, NGS technique could detect various mutation variants affecting collagen genes and non-collagen genes which demonstrated that increase incidence of autosomal recessive form of osteogenesis imperfecta with absence of family history of repeated fractures. Randomly selected cases from different destinations in upper Egypt give a chance to detect variants affecting patients in this area. We use multiple DNA primers for the detection of gene mutations in our studied children as no research was done in upper Egypt before for patients with osteogenesis imperfecta.