Berardinelli-Seip syndrome

Berardinelli-Seip syndrome, also known as congenital generalized lipodystrophy (CGL), is a rare genetic disorder characterized by lipoatrophy, acromegaloid features, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis. With estimated prevalence 1 in every 10,000,000 births, CGL challenges medical specialists to seek better ways for early diagnosis of the disease. Despite its rarity, the condition is associated with severe metabolic and cardiovascular complications, leading to significant morbidity and reduced life expectancy. Advances in molecular genetics have identified mutations in AGPAT2, BSCL2, CAV1, and PTRF, which provide important insights into adipose tissue biology and systemic metabolism. Early recognition and genetic confirmation are crucial to initiate timely interventions, including lifestyle modification, insulin sensitizers, and lipid-lowering therapies including metreleptin therapy in indicated cases. Two illustrative cases are presented, reflecting our experience with the clinical variability, genetic findings, and therapeutic strategies in CGL as well as highlighting the importance of comprehensive care and emerging therapies.