SIM1 and obesity due to melanocortin 4 receptor deficiency: At the other end of the spectrum lies the case of extreme obesity, mostly since birth, and here again germ line transmission in genetic alterations was noted in leptin (LEP), leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), melanocortin 4 receptor (MC4R), single-minded homolog 1 (SIM1), brain-derived neurotrophic factor (BDNF), and its receptor TrkB coded by neurotrophic tyrosine kinase receptor type 2 gene (NTRK2) reviewed in [11].