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]. The gene discussed is SIM1; the disease is obesity disorder.