Considering these data, we aimed to (i) specify the methylation signature in PWS and PWS-related syndromes by considering a group with different mutations of the 15q11–q13 region including SNORD116 MD and MAGEL2 mutation, (ii) associate the signatures with biological pathways and clinical features and (iii) specify the methylation signatures with the two mutations of SNORD116 MD and MAGEL2. Here, MAGEL2 is linked to Prader-Willi syndrome.