Pten Hamartoma Tumor Syndrome

PTEN hamartoma tumor syndrome (PHTS) is a term defining a group of clinically heterogeneous disorders united by a germline PTEN mutation and the involvement of derivatives of all 3 germ cell layers, manifesting with hamartomas, overgrowth and neoplasia. Currently, subsets carrying clinical diagnoses of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes and SOLAMEN syndrome (see these terms) belong to PHTS.

Epidemiology

The prevalence is unknown.

Clinical description

Disease onset depends on the specific disorder. The most important component seen in this group are malignancies and include breast carcinomas in women with an 85% lifetime risk, epithelial thyroid carcinomas with a 35% lifetime risk, endometrial carcinomas with a 28% lifetime risk, renal cell carcinomas with a 32% lifetime risk and colorectal carcinoma with a 10% lifetime risk. Epithelial thyroid cancer has been diagnosed before the age of 18 years and as early as 6 years of age. Non-malignant components of PHTS vary but include macrocephaly (in >90% of individuals), benign thyroid pathology (especially Hashimoto thyroiditis), mucocutaneous hamartomas, colonic polyps (in >90% of individuals who have received a colonoscopy) and vascular malformations.

Etiology

By definition, all individuals with PHTS carry germline mutations in the phosphatase and tensin homolog PTEN gene. The canonical PTEN pathway antagonizes phosphoinositide 3-kinase (PI3K) and downregulates P-AKT resulting in control of the cell cycle, apoptosis, migration and genome stability. There are other additional non-canonical functions of PTEN.