Monogenic obesity in a familial cluster: insights into laurence-moon-bardet-biedl syndrome and leptin deficiency associated with genetic variants in BBS12 and LEPR genes

Abstract

Monogenic obesity is a rare but clinically significant condition characterized by excessive weight gain due to genetic mutations that affect appetite regulation and energy balance. This case series explores the clinical presentation and genetic underpinnings of monogenic obesity in a familial cluster, focusing on Laurence-Moon-Bardet-Biedl Syndrome (LMBBS) and leptin deficiency associated with genetic variants in the BBS1 and LEPR genes. The index patient, an 11-year-old female, presented with progressive weight gain since infancy, accompanied by acanthosis nigricans on the neck and axillary region. Genetic testing revealed mutations in both the BBS1 and LEPR genes, confirming a monogenic etiology of obesity. Remarkably, her two siblings and a cousin from the paternal side exhibited similar clinical profiles and shared the same genetic variants. This report shows the significance of genetic testing in diagnosing monogenic obesity disorders and highlights the familial clustering observed in such cases. The findings emphasize the need for heightened awareness and consideration of genetic factors in the evaluation of obesity, particularly in pediatric patients with a family history suggestive of monogenic obesity.