Similar to previous reports [25, 26] our patients showed a bimodal way of presentation: younger pediatric subjects seeking for medical advice because of early-onset obesity and/or congenital hypothyroidism had more often structural gene mutations, suggesting a more severe impairment of the Gsα protein, not only in endocrine organs as reported by prior functional studies [27], but probably also in adipose tissue. This evidence concerns the gene GNAS and obesity due to melanocortin 4 receptor deficiency.