PTEN: One Gene, Many Syndromes

PTEN, on 10q23.3, encodes a major lipid phosphatase which signals down the phosphoinositol-3-kinase/Akt pathway and effects G1 cell cycle arrest and apoptosis. Germline PTEN mutations have been found to occur in 80% of classic Cowden syndrome (CS), 60% of Bannayan-Riley-Ruvalcaba syndrome (BRRS), up to 20% of Proteus syndrome (PS), and approximately 50% of a Proteus-like syndrome (PSL). CS is a heritable multiple hamartoma syndrome with a high risk of breast, thyroid, and endometrial carcinomas. BRRS is a congenital autosomal dominant disorder characterized by megencephaly, developmental delay, lipomatosis, and speckled penis. PS and PSL had never been associated with risk of malignancy. Finding germline PTEN…