Molecular Genetic Study of Suspected Cases of Osteogenesis Imperfecta Attending Assiut University Children Hospital

Osteogenesis imperfecta is a genetic disorder of the connective tissue matrix caused by abnormal collagen microfibril assembly, .Several clinical subtypes of Osteogenesis imperfecta have been described based on the clinical, biochemical, and molecular nature of the disorder . New research is emphasizing the structural interaction within the microfibril and identifying regions within the collagen, which play greater or lesser roles in the structural properties of the triple helix, .In taking this information into account, clinical phenotypes resulting from certain mutations can be predicted because of this pathogenetic correlation.

The clinical manifestations vary considerably, ranging from a severe perinatal lethal form to a mild disorder which only becomes evident in adulthood, manifesting as premature osteoporosis, .Most commonly, however, Osteogenesis imperfecta presents in childhood with multiple fractures and related complications, .The precise incidence of Osteogenesis imperfecta is unknown and reports vary from approximately 1/100,000 to 1/25,000 dependent on the criterion used to define Osteogenesis imperfecta.

Severe forms and milder disease occur with approximately similar incidence. 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 Osteogenesis imperfecta are common to other disorders of connective tissues; hyper-mobile joints and a blue sclera are among these features frequently described, The incorporation of abnormal type 1 collagen in teeth results in brittle opalescent teeth, the hallmark of Dentinogenesis Imperfecta, often seen in Osteogenesis imperfecta, .Progressive conductive hearing loss in early adulthood is the result of damage to the ossicles in the middle ear; over time, hearing loss typically progresses and combined conductive and sensorineural hearing loss may be seen in adults, similar to that of otosclerosis. Short stature and bone deformity are common features of the disorder The mainstay of treatment is orthopedic management along with physiotherapy, Bisphosphonates are being evaluated for efficacy and clinical trials have shown improvement at least in bone mineral density

Disorders associated with fragility fractures in children:

A) Primary conditions