Rare genetic forms of obesity in childhood and adolescence, a comprehensive review of their molecular mechanisms and diagnostic approach

Obesity represents a major health problem in the pediatric population with an increasing prevalence worldwide, associated with cardiovascular and metabolic disorders, and due to both genetic and environmental factors. Rare forms of obesity are mostly monogenic, and less frequently due to polygenic influence. Polygenic form of obesity is usually the common obesity with single gene variations exerting smaller impact on weight and is commonly non-syndromic.Non-syndromic monogenic obesity is associated with variants in single genes typically related to the hypothalamic leptin-melanocortin signalling pathway, which plays a key role in hunger and satiety regulation, thus body weight control. Patients with these genetic defects usually present with hyperphagia and early-onset severe obesity. Significant progress in genetic diagnostic testing has recently made for early identification of patients with genetic obesity, which guarantees prompt intervention in terms of therapeutic management of the disease.

Automated summary

Obesity is a major health issue in children worldwide, caused by both genetic and environmental factors. Rare forms of obesity are mainly caused by single gene variations, while polygenic obesity is more common and less severe. Non-syndromic monogenic obesity is associated with single gene variations in the leptin-melanocortin signaling pathway, which regulates hunger and satiety. Advances in genetic diagnostic testing have enabled early identification and intervention for patients with genetic obesity.