Alterations of components of the cAMP/PKA pathway, including somatic variants in PRKACA (encoding for the catalytic subunit of the protein kinase A) and GNAS (encoding for the stimulatory G protein alpha-subunit), have been identified as causative factors for up to 50–60% of CPA associated with CS (CPA-CS) [8, 9]. This evidence concerns the gene GNAS and Cowden syndrome 1.