PTEN hamartoma tumor syndrome

PTEN hamartoma tumor syndrome (PHTS) is the molecular diagnostic term describing patients with Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and other clinical presentations with germline mutation of the PTEN tumor suppressor gene. PHTS confers increased risks for specific malignancies, most notably breast, thyroid, renal, and endometrial cancers. Benign tumors are common, affecting a variety of tissues, and can range from subtle skin papules requiring no treatment to devastating vascular anomalies. There is also a broad range of neurodevelopmental effects, with some patients having no challenges and others with severe autism spectrum disorder and mental retardation. While most cases are inherited in a family for generations, following an autosomal dominant pattern, at least 10% and perhaps as many as 44% of cases are due to a new (de novo) mutation. Clinical presentations can vary dramatically from patient to patient, even among those in the same family. Features of this condition that may assist in diagnosis prior to cancer development can be subtle and difficult to recognize. This chapter will help the reader identify which patients should be referred for genetics evaluation and how to manage patients diagnosed with this rare condition.