Mutations in GNAS have long been known to inhibit GTPase activity of the Gαs subunit and thereby cause constitutive Gαs activation, abnormal cAMP signaling, endocrine hyperfunction, and tumor formation; postzygotic GNAS mutations are found in McCune–Albright syndrome, which can be associated with CS (72, 73). Here, GNAS is linked to Cowden syndrome 1.