Clinical Genetics of Human Osteogenesis Imperfecta (OI): An Updated Review

Abstract

The hallmark of Osteogenesis imperfecta (OI) is a predisposition to bone fractures, which can range in severity from somewhat increased fracture frequency to birth traumas. In 1788, OI was first described scientifically. Since then, the adoption of bisphosphonate therapy, the identification of abnormalities in collagen type I biosynthesis as the primary cause of most cases of OI, and the classification of OI into four categories (the "Sillence classification") have all been significant turning points in the research and treatment of OI. Additionally, over the last five years, it has become evident that OI is a collection of diverse disorders, with 10% of cases thought to be caused by causative recessive variants in the 21 known genes and 90% of cases thought to be caused by causative dominant variants in the COL1A1 or COL1A2 genes. This review aims to highlight the current knowledge about the clinical, genetic and molecular analysis of the OI types has been presented comprising 23 genes with different location on chromosomes. Concerned family doctors, researchers and pediatricians may find this review useful in assessing and treating OI in children at the outset. It also provides a summary of the complex molecular mechanism responsible for the OI and might be helpful in genetic counseling and rapid genetic identification.