We postulate an evolving hypothalamic dysregulation to explain this previously unrecognised biphasic phenomenon: any brain injury may disrupt the hypothalamic ‘brake’ and GnRH pulse generator to cause CPP in a prepubertal population, but wider disease and further injury due to progressions and further local treatments to this area may cause Gn deficiency in a peri- or post-pubertal cohort. This evidence concerns the gene GNRH1 and mucopolysaccharidosis type 3D.