The Clinical Spectrum of <i>PTEN</i> Mutations.

Abstract

<i>PTEN</i> is a tumor suppressor gene that classically dampens the PI3K/AKT/mTOR growth-promoting signaling cascade. <i>PTEN</i> dysfunction causes dysregulation of this and other pathways, resulting in overgrowth. Cowden syndrome, a hereditary cancer predisposition and overgrowth disorder, was the first Mendelian condition associated with germline <i>PTEN</i> mutations. Since then, significant advances by the research and medical communities have elucidated how clinical phenotypic manifestations result from the underlying germline <i>PTEN</i> mutations. With time, it became evident that <i>PTEN</i> mutations can result in a broad phenotypic spectrum, causing seemingly disparate disorders from cancer to autism. Hence, the umbrella term of <i>PTEN</i> hamartoma tumor syndrome (PHTS) was coined. Timely diagnosis and understanding the natural history of PHTS are vital because early recognition enables gene-informed management, particularly as related to high-risk cancer surveillance and addressing the neurodevelopmental symptoms.