Although the Bardet-Biedl syndrome (BBS: severe obesity, polydactyly, learning disabilities, retinopathy, renal disease and cardiac malformations) was described more than 80 years ago, it is only over the past few years that extensive data on the natural history and molecular pathogenesis of this complex disorder have been reported. We now know that BBS can be caused by mutations in at least 12, genes and, although it is typically inherited in an autosomal recessive pattern, BBS may occasionally exhibit more complex inheritance. In this study, we are defining the physical (body mass, percent and distribution of body fat) and metabolic (hyperglycemia, hyperinsulinemia, serum levels of lipids and adipokines) characteristics of glucose and fat metabolism in a cohort of adult and pediatric patients with BBS. We are also characterizing the hypogenitalism in BBS, and attempting to determine its relationship, if any, to the incidence of obesity in BBS. In addition, we are studying the retinal dystrophy, the renal dysfunction, and the nature of the reported mental retardation/learning disability that is found in many patients. We plan to correlate the phenotypic manifestations in our subjects with the results of our mutation analysis studies. Our objective is to learn more about the genetic alterations that may underlie the obesity and associated organ dysfunction that characterizes BBS.