Figure 2. From a controlled epigenetic silencing to loss of silencing and reactivation of the maternal alleles of PWS genes. This scheme summarizes the quantity of transcripts produced from the maternal and paternal inherited alleles of PWS genes such as NECDIN (NDN) and MAGEL2 in a normal individual (A), in PW patients (B and C), or in perspective of a pharmacological therapy (D). In a normal individual, chromosomal 15q11-q13 regions from both parental origins are present, and transcripts issued only from the paternal allele of PWS genes are detected (A). In PW patients, due to a mutation of the 15q11-q13 region, there are no “PWS transcripts” issued from the paternal active allele (B, C, and D). However, a stochastic partial loss of silencing of the maternal alleles, named here epigenetic flexibility, may result in the production of few maternal “PWS transcripts” detected in some patients (C). We postulate that chemical compounds might modify this epigenetic flexibility in PW patients, allowing an increased expression of the maternal “PWS transcripts” and consequently alleviating the PWS features (D).