The authors present the special case of a 12-year-old boy with early-onset severe obesity determined by a pathogenetic mutation in the SIM1 gene, in which it has been hypothesized how the cumulative effects of other genetic variants detected in melanocortin pathway genes determine the complex clinical picture that includes partial diabetes insipidus, transient metabolic complications, and neurobehavioral disorders. The gene discussed is SIM1; the disease is obesity due to melanocortin 4 receptor deficiency.