Cowden syndrome: a novel mutation and overlooked glycogenic acanthosis in gingiva

Abstract

Conflicts of interest: none declared. Cowden syndrome (CS; OMIM 158350) is a rare genetic disorder that is characterized by multiple hamartomas (affecting various organs derived from all three germ layers) and an increased risk of some cancers, in particular thyroid and breast cancers.1 The lifetime risks for thyroid and breast cancer are estimated to be 3–10% and 25–50%, respectively.1 Characteristic mucocutaneous manifestations include multiple facial trichilemmomas, oral mucosal papillomatoses and acral keratoses. These clinical findings, as well as other hamartomatous or carcinomatous lesions, usually become evident in adulthood. CS is caused by mutations in the PTEN gene (phosphatase and tensin homologue deleted from chromosome 10), which encodes a dual phosphatase that signals down the phosphoinositol‐3‐kinase/Akt pathway and exerts G1 cell cycle arrest and apoptosis.1,PTEN mutations also cause a subset of Bannayan–Riley–Ruvalcaba syndrome (BRRS; OMIM 153480).1 BRRS has not been associated with malignant lesions. It was proposed that CS and BRRS result from germline mutations in a common gene (PTEN), and thus should be classified as PTEN hamartoma tumour syndromes (PHTS). The genetic mechanism by which mutations in a single gene cause such a diverse number of phenotypes is largely unknown. Here, we report a novel single nucleotide duplication in the PTEN gene in a de novo case of CS, in which mutational analysis was helpful in confirming the clinical diagnosis. Interestingly, in this case, the histopathological findings of mucosal papillomatosis contrasted with those that are generally recognized in cases of CS.