Specifically, a broad spectrum of metabolic phenotypes, including obesity/overweight, fasting hyperglycemia, and insulin resistance, has previously been reported in IHH individuals harboring rare damaging heterozygous SNVs in KLB, the gene encoding for β-klotho [67], and rare digenic LoF variants in FGFR1 and KLB have been reported in patients with severe insulin resistance [68]. Here, FGFR1 is linked to obesity due to melanocortin 4 receptor deficiency.