A Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features, and Molecular Diagnosis.

Abstract

Background: Syndromic forms of obesity are uncommon, complicated illnesses that include early-onset obesity along with other clinical characteristics such as organ-specific abnormalities, dysmorphic symptoms, and intellectual incapacity. These syndromes frequently have a strong genetic foundation, involving copy number variations, monogenic mutations, and chromosomal abnormalities.

Methods: Using terms like "syndromic obesity," "genetic diagnosis," and "monogenic obesity," a comprehensive literature search was conducted to find articles published between 2000 and 2025 in PubMed, Scopus, and Web of Science. Peer-reviewed research addressing the clinical, molecular, or genetic aspects of syndromic obesity were among the inclusion criteria. Conference abstracts, non-English publications, and research without genetic validation were among the exclusion criteria. The whole genetic, clinical, diagnostic, and therapeutic domains were thematically synthesized to create a thorough, fact-based story. Research using chromosomal microarray analysis (CMA), whole-exome sequencing (WES), next-generation sequencing (NGS), and new long-read sequencing platforms was highlighted.

Results: Despite the fact that molecular diagnostics, especially NGS and CMA, have made tremendous progress in identifying pathogenic variants, between 30 and 40 percent of instances of syndromic obesity are still genetically unexplained. One significant issue is the variation in phenotype across people with the same mutation, which suggests the impact of environmental modifiers and epigenetic variables. In addition, differences in access to genetic testing, particularly in areas with limited resources, can make it difficult to diagnose patients in a timely manner. Additionally, recent research emphasizes the possible contribution of gene-environment interactions, gut microbiota, and multi-omic integration to modifying disease expression.

Conclusions: Syndromic obesity is still poorly understood in a variety of groups despite significant advancements in technology. Multi-layered genomic investigations, functional genomic integration, and standardized diagnostic frameworks are necessary to close existing gaps. The development of tailored treatment plans, such as gene editing and focused pharmaceutical therapies as well as fair access to cutting-edge diagnostics are essential to improving outcomes for people with syndromic obesity.