Monogenic and Syndromic Causes of Obesity

Abstract

Obesity is a pediatric and adult global health problem of epidemic proportions in westernized societies. It results from imbalance of energy intake and expenditure. The cause of obesity is heterogeneous with complex biological processes playing a role including control of peptides involved in regulating appetite, cellular energy and metabolism, and fat production influenced by environmental interactions. Advances in genetic technology have led to discoveries of single gene and copy number variants playing a role in early onset of severe obesity and other obesity phenotypes. Heritability studies have shown that genetic components can contribute to 40–70% of obesity with over 350 potential genes reported in the literature. Monogenic causes of obesity and dozens of syndromic examples are discussed such as Prader-Willi syndrome, in which individuals develop obesity due to hyperphagia and decreased resting energy expenditure. The current knowledge of monogenic and syndromic causes of obesity, their genotype, and clinical features are summarized with descriptions. The genetic dissection of obesity with characterization of biological pathways and gene-protein environmental interactions at the brain level will contribute to understanding disease mechanisms and outcomes. This information can be applied for early diagnosis, prevention, and treatment as well as elucidating therapeutic targets for development of personalized medicines designed for obesity in humans.KeywordsObesityMonogenic and syndromic causesSingle gene and copy number variantsBiological processes, energy regulation, and inheritanceIllustrations