The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This group of disorders shares significant clinical overlap.
CS is characterized by increased risk for both benign and malignant tumors of the breast, thyroid, and endometrium. Affected individuals have macrocephaly and almost all will develop the pathognomonic mucocutaneous lesions by the third decade of life, including trichilemmomas, papillomatous papules, and acral and plantar keratoses. Affected females also have a high rate of benign breast disease. Hamartomatous polyposis of the GI tract can be observed, but is rarely symptomatic.
BRRS is a congenital disorder characterized by macrocephaly, intestinal polyposis, lipomas, and enlargement and spotty pigmentation of the glans penis. Other common features may include: high birth weight, mild to severe mental retardation with delayed motor and speech development, proximal muscle weakness, joint hyperextensibility, macrodactyly, pectus excavatum, and scoliosis. Hamartomatous GI polyps are observed in ~45% of affected individuals. The cancer risks in patients with BRRS who harbor PTEN gene mutations are thought to be similar to that of individuals with CS.
PS/PS-like (PSL) is an extremely rare congenital disorder with generalized, unilateral, or localized hamartomatous overgrowth of any tissue. Unusual malignancies have been observed, such as cystadenoma of the ovary, testicular tumors, central nervous system tumors, and parotid monomorphic adenomas.