| 42 43 | See page 67 for references PTEN gene summary PTEN hamartoma tumor syndrome Gene name PTEN Associated syndrome PTEN hamartoma tumor syndrome Primary associated cancers Breast, endometrial, colorectal, thyroid Frequency 1 in 200,000 Inheritance pattern Autosomal dominant Overview · ·There are four clinically distinct syndromes associated with mutations in PTEN, including Cowden syndrome. · ·In addition to an increased cancer risk, those with a PTEN mutation generally develop non-cancerous (benign) tumors throughout the body known as hamartomas. · ·Thyroid disease, including benign multinodular goiter, adenomatous nodules, and follicular adenomas have been reported in approximately 30%–68% of adults with a PTEN mutation. About the PTEN hamartoma tumor syndrome (PHTS) PHTS is characterized by hamartomatous tumors and mutations in the PTEN gene. There are four clinically distinct syndromes: Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome. · ·Cowden syndrome is a multiple hamartoma syndrome with a high risk for benign and malignant tumors of the thyroid, breast, and endometrium, as well as elevated risk for renal cell carcinoma and colon cancer. · ·Bannayan-Riley-Ruvalcaba syndrome is a disorder characterized by macrocephaly, intestinal polyposis, lipomas, and pigmented macules of the glans penis. · ·Proteus syndrome is a complex, highly variable disorder involving overgrowth of multiple tissues. · ·Proteus-like syndrome is undefined but manifests with similar overgrowth manifestations. POLE · ·For men and women: · ·Colonoscopy beginning at age 25–30 years. · ·If negative, repeat every 2–3 years. · ·If polyps are found, repeat every 1–2 years. · ·Surgical evaluation and consideration of colectomy if polyp burden becomes unmanageable by colonoscopy. · ·Consider gastroduodenoscopy (endoscopy of the stomach and upper portion of the small bowel) every 3 years. POLD1 · ·For men and women: · ·Colonoscopy beginning at age 25–30 years. · ·If negative, repeat every 2–3 years. · ·If polyps are found, repeat every 1–2 years. · ·Surgical evaluation and consideration of colectomy if polyp burden becomes unmanageable by colonoscopy. · ·Consider gastroduodenoscopy every 3 years. · ·For women: · ·Education regarding early signs of uterine cancer, such as unexplained or heavy bleeding. · ·Beginning at age 40, annual endometrial cancer screening, such as endometrial sampling. · ·Hysterectomy (removal of the uterus) may also be considered. There are reported cases of individuals who inherit mutations in both copies of the POLE gene and have a rare condition called FILS (facial dysmorphism, immunodeficiency, livedo, and short stature) syndrome. There are very few known cases of FILS syndrome and the exact prevalence of FILS is unknown. However, for individuals who test positive for a POLE mutation, it may be appropriate to consider carrier screening for POLE mutations in a spouse or partner.