GH1 and hereditary disease: In summary, some children labeled as ISS may have a low spontaneous GH secretion that has not been detected, a genetic disorder that has not been studied (e.g. SHOX haploinsufficiency), a dysfunctional GH promoter or an abnormal GH molecule that has not been analyzed, or some form of decreased responsiveness to GH by a genetic defect in GH signaling.