A Novel PTEN Mutation in a Korean Patient with Cowden Syndrome and Vascular Anomalies

Abstract

Cowden syndrome (CS; OMIM #158350) is a rare autosomal dominant disorder characterized by multiple hamartomas of ectodermal, mesodermal and endodermal origins. CS patients have a high risk of developing breast, thyroid and endometrial cancers (1). Typical mucocutaneous symptoms include facial trichilemmomas (hamartomas of the infundibulum of the hair follicle), acral keratoses and mucocutaneous papules. Other mucocutaneous lesions include dermal fibromas, scrotal tongue and skin tags (2). Additional disease features may include adult-onset Lhermitte-Dulclos disease (LDD) (a dysplastic gangliocytoma of the cerebellum), macrocephaly, mental retardation and structural malformations in the genitourinary system (3). This list has recently been revised (4). PTEN is a tumor suppressor gene located on chromosome 10q23.3. It encodes a phosphatase that influences the cell cycle, causing G1 arrest and apoptosis (5). PTEN hamartoma tumor syndromes (PHTS) are a group of disorders characterized by PTEN mutations and hamartomas of multiple organ systems. They include CS, Bannayan-Riley-Ruvalcaba syndrome (BRRS; OMIM #153480), Proteus syndrome, and Proteus-like syndrome (6). Some 85% of CS patients carry germline loss-of-function mutations in the PTEN gene. Among PHTS, it has been reported that BRRS and CS share clinical characterisitics and represent a single entity. However, BRRS can be clinically differentiated from CS by hamartous polyposis, macrocephaly, lipomatosis, hemangioma and a speckled penis.