Diagnostic Approach to Genetic Obesity in Children: From Pathophysiology to Precision Medicine-A Narrative Review.
- 1Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Ospedale Maggiore della Carità, 28100 Novara, Italy.
- 2Department of Pediatrics, IRCCS San Raffaele Hospital, 20132 Milan, Italy.
Abstract
Childhood obesity is a major global health concern with a strong heritable component. While most cases are polygenic and environmentally driven, a subset of children present with rare genetic forms of obesity, including syndromic and monogenic disorders. Over the past three decades, advances in gene discovery-from candidate gene studies to genome-wide association studies (GWAS) and next-generation sequencing (NGS)-have significantly improved our understanding of the biological pathways regulating appetite and energy balance, particularly the leptin-melanocortin pathway. Early identification of genetic obesity is clinically relevant, as it allows for tailored management, targeted pharmacological interventions, genetic counseling, and a reduction in psychosocial stigma. However, distinguishing rare genetic obesity from common polygenic obesity remains challenging in clinical practice. This narrative review summarizes the current knowledge on the genetic architecture of pediatric obesity, explores the transition from gene discovery to precision medicine, discusses available diagnostic algorithms and genetic testing strategies, and proposes an updated diagnostic flowchart. In a more clinically useful model, genetic obesity is not defined solely by the presence or absence of a pathogenic variant, but as a continuum in which phenotype, genetic variants, age, and environmental exposure interact and define risk prediction and therapeutic strategies, especially in the pediatric population.
Related
- Glucocorticoids in the Management of Bronchial Asthma: From Pathophysiology to Precision Medicine
- Chronic Venous Disease in Pregnancy: Pathophysiology, Diagnostic Pitfalls, and a Trimester-Stratified Management Framework—A Narrative Review
- Individualized dosing in the precision medicine era: a narrative review
- Avoidant/Restrictive Food Intake Disorder in Children and Adolescents: Nutritional Risk, Diagnostic Boundaries, and Multidisciplinary Care—A Narrative Review
- Precision Medicine in Epilepsy: Diagnostic Yield by Next-Generation Sequencing and Genotype–Phenotype Findings in a Romanian Cohort
BibTeX
@article{partenope2026diagnostic,
title = {{Diagnostic Approach to Genetic Obesity in Children: From Pathophysiology to Precision Medicine-A Narrative Review.}},
author = {Cristina Partenope and Ivana Rabbone and Roberta Pajno},
journal = {Medicina (Kaunas, Lithuania)},
year = {2026},
month = sep,
doi = {10.3390/medicina62101850},
url = {https://europepmc.org/article/MED/42942381},
note = {CC BY},
}
RIS
TY - JOUR
TI - Diagnostic Approach to Genetic Obesity in Children: From Pathophysiology to Precision Medicine-A Narrative Review.
AU - Cristina Partenope
AU - Ivana Rabbone
AU - Roberta Pajno
PY - 2026
DA - 2026/09/24
JO - Medicina (Kaunas, Lithuania)
DO - 10.3390/medicina62101850
UR - https://europepmc.org/article/MED/42942381
AB - Childhood obesity is a major global health concern with a strong heritable component. While most cases are polygenic and environmentally driven, a subset of children present with rare genetic forms of obesity, including syndromic and monogenic disorders. Over the past three decades, advances in gene discovery-from candidate gene studies to genome-wide association studies (GWAS) and next-generation sequencing (NGS)-have significantly improved our understanding of the biological pathways regulating appetite and energy balance, particularly the leptin-melanocortin pathway. Early identification of genetic obesity is clinically relevant, as it allows for tailored management, targeted pharmacological interventions, genetic counseling, and a reduction in psychosocial stigma. However, distinguishing rare genetic obesity from common polygenic obesity remains challenging in clinical practice. This narrative review summarizes the current knowledge on the genetic architecture of pediatric obesity, explores the transition from gene discovery to precision medicine, discusses available diagnostic algorithms and genetic testing strategies, and proposes an updated diagnostic flowchart. In a more clinically useful model, genetic obesity is not defined solely by the presence or absence of a pathogenic variant, but as a continuum in which phenotype, genetic variants, age, and environmental exposure interact and define risk prediction and therapeutic strategies, especially in the pediatric population.
SN - 1010-660X
SN - 1648-9144
ER -