Germline mutations in PTEN have been reported in a variety of rare PHTS conditions and have also been found in previously undiagnosed individuals with isolated PHTS-related phenotypes (e.g., autism spectrum disorder with macrocephaly [23], breast cancer [24] and differentiated thyroid cancer [25]), suggesting that PHTS may be underdiagnosed [7]. Here, PTEN is linked to PTEN hamartoma tumor syndrome.