Genotype-Phenotype Spectrum of Non-Syndromic Monogenic Obesity in a National Paediatric Cohort

The authors aimed to clarify the genotype-phenotype and metabolic correlations of non-syndromic monogenic obesity caused by defects in the leptin-melanocortin pathway in a national pediatric cohort. They found that biallelic variants in LEPR and monoallelic variants in MC4R were the most common causes of severe obesity, with distinct metabolic profiles and growth impairments associated with these genotypes. The study highlights the need for early diagnosis and risk stratification based on genetic findings, particularly for those with more severe metabolic outcomes.