A new homozygous pathogenic LEPR variant causing severe, early onset obesity in a Senegalese child.

We report the case of a three-year-old Senegalese child presenting with severe obesity and hyperphagia since birth. Despite normal birth parameters and non-consanguineous parents with average BMI, the child exhibited rapid weight gain, surpassing obesity thresholds before the age of one. Genetic analysis revealed a novel homozygous variant in the LEPR gene (c.3190 G>T; p.(Glu1064Ter)). Functional assays demonstrated impaired leptin receptor signaling due to this truncating mutation. This case highlights the importance of considering monogenic causes in early-onset obesity. Identifying specific mutations enables the proposal of targeted therapies and the adaptation of clinical management.