Nine susceptibility genes, determinants of non-syndromic Mendelian forms of human obesity, are involved in the hypothalamic control of energy balance via the leptin-melanocortin pathway and/or in neural development [4]: brain-derived neurotrophic factor (BDNF), leptin (LEP), leptin receptor (LEPR), melanocortin-4 receptor (MC4R), neurotrophic tyrosine kinase receptor type 2 (NTRK2), prohormone convertase 1 (PCSK1), proopiomelanocortin (POMC), single-minded homolog 1 (SIM1) and, more recently, melanocortin 2 receptor accessory protein 2 (MRAP2) [7]. The gene discussed is SIM1; the disease is obesity due to melanocortin 4 receptor deficiency.