Cowden Syndrome

Abstract

Abstract Cowden syndrome (CS) is a multiple hamartoma syndrome characterized by high risks of benign and malignant tumours of the thyroid, breast, kidney, and endometrium, as well as neurodevelopmental disorders such as autism spectrum disorder (ASD). Affected individuals typically have macrocephaly at birth, and mucocutaneous features evident by the late 20s. The tumour suppressor gene PTEN, encoding an ubiquitously expressed phosphatase classically counteracting the PI3K/AKT/mTOR growth-promoting cascade, is the first and currently only clinically actionable CS susceptibility gene. Individuals with germline PTEN mutations have diverse phenotypes, can have different syndromic names, and fall under the umbrella term PTEN hamartoma tumour syndrome (PHTS). Ongoing investigations in the research arena are uncovering other susceptibility genes in PTEN mutation-negative patients. Clinicians play a critical role in recognizing ‘red flag’ signs and symptoms to establish a CS diagnosis. Timely diagnosis is key, as early recognition enables high-risk cancer surveillance and related medical management.