The transition of DS to HO is related to age and correlates with (age-dependent) maturation of the hypothalamus, 2) CPP in these children is the direct consequence of activation of the GnRH pulse generator by increased pressure due to tumor location or hydrocephalus and not a consequence of obesity, 3) Pituitary deficiencies are prevalent in children who develop HO. Here, GNRH1 is linked to obesity due to melanocortin 4 receptor deficiency.