Several efforts were made to find a correlation between the degree of GNAS epigenetic defects and the severity of the disease in terms of age at diagnosis (as a marker of disease precocity), the number or degree of hormonal resistances and the number of AHO symptoms; however, no explanation for the phenotypic heterogeneity in iPPSD3 was found [11, 13, 14]. This evidence concerns the gene GNAS and pseudohypoparathyroidism type 1A.