MC4R and hyperinsulinism: In addition to severe early-onset obesity and hyperphagia — the hallmark features — pathogenic MC4R variants have also been linked to accelerated linear growth during childhood (but normal final height), hyperinsulinemia, lower total and LDL-cholesterol levels, increased lean body mass and increased bone mineral density [10, 22, 28, 29]. Interestingly, both hyperinsulinemia and hyperphagia associated with MC4R deficiency appear to be age-dependent, tending to diminish over time, with the underlying mechanisms remaining unclear [22].