Therefore, children with ALS mutations may have reduced serum IGF-1 and even lower IGFBP-3 concentrations, as well as mild growth failure and delayed puberty.32 Heterozygous variants are responsible for isolated short stature.33 In fact, heterozygous carriers seem to be shorter than siblings and present lower levels of IGF-1, IGFBP-3 and ALS; delayed puberty is frequently observed in these patients, typically in males.33 This evidence concerns the gene IGFBP3 and amyotrophic lateral sclerosis.