ISS is defined as a height more than two standard deviations (SD) below the age-, sex-, and population-matched mean, despite a normal or increased response to growth hormone (GH) on the GH stimulation test, and in the absence of any systemic, endocrine or metabolic disease, chromosome abnormality, or other disease that may compromise growth [2, 3]. This evidence concerns the gene GH1 and Other metabolic disease.