Pediatric genetic obesity: From molecular pathophysiology to precision therapeutics

Abstract

Childhood obesity results from a spectrum of genetic contributors, ranging from monogenic leptin-melanocortin pathway defects and syndromic causes to polygenic predisposition. Early recognition of red flags—severe onset before the age of 5 years, extreme hyperphagia, consanguinity, or dysmorphic features—should prompt biochemical and genetic evaluation, since a growing number of these conditions now have targeted pharmacotherapy. This chapter outlines a practical approach to clinical screening, biochemical work-up, and tiered genetic testing for suspected monogenic or syndromic obesity, along with an overview of precision and broader pharmacologic options, and offers guidance on when affected children should be referred to a pediatric endocrinologist.