PTEN hamartoma tumor syndrome defines a spectrum of multi-system disorders caused by PTEN gene alterations, including Cowden syndrome, Bannayan Riley Ruvalcaba syndrome, PTEN-related proteus syndrome and Proteus-like syndrome and so on.[20] The characteristic change in PTEN hamartoma tumor syndrome is the appearance of multiple hamartomas, commonly seen in the skin and digestive tract, which can manifest as papular changes in the facial skin, papillary changes in the oral mucosa, acrokeratosis, and gastrointestinal polyps. Here, PTEN is linked to Cowden disease.