Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder of bone. The phenotypes range from lethal in the perinatal period to an extremely mild presentation with rare fractures. The majority of affected individuals have mutations in the two type I collagen genes, COL1A1 and COL1A2 but about 10-15% have mutations in other genes, none of which have yet been identified or characterized. To date, both research interest and clinical concern have centered around the severe forms in which early death or severe disability are the rule. Treatment trials are in process to identify medical therapies that may alter the character of bone that results when structurally abnormal collagens are synthesized. These therapies include the use of bisphosphonates to slow bone turnover, and cell replacement, all, to date, with uncertain therapeutic efficacy. Gene therapeutic approaches, including inactivation of the mutation bearing alleles provides another line of investigation with the underlying idea being to convert a severe form of OI to a milder form that results from haploinsufficiency. This approach assumes that the natural history of 'haploinsufficiency is well known, that therapies will be effective, and that outcomes can be predicted. Surprisingly, although the majority of the estimated 20-40,000 people in the US with OI have the mild forms of the condition, the natural history is not well appreciated, the frequency of major complications remains uncertain, the prospects for effective therapies remains unexplored, and the fiscal impact of the disorder on the family and the US health care system remain uncharacterized. To examine these and related issues, a one -day meeting """"""""Mild OI - Toward Better Understanding and Treatment"""""""" chaired by Peter Byers, MD and Michael Whyte, MD will be held in Chicago on April 19, 2004, in conjunction with the ASCI and AAP meetings. This meeting will bring together 25 investigators to examine how further study of individuals and families with mild forms of OI will provide greater insight into the heterogeneity and underlying defects in this and related disorders and develop an approach to their assessment and treatment that mirrors the attention currently being paid to the more severe forms.
