PTEN Hamartoma Tumor Syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba (BRR), Proteus syndrome (PS), and Proteus-like syndrome. CS is characterized by benign and malignant tumors of the breast, thyroid, and endometrium.
Individuals with CS typically have macrocephaly and have an increased chance for developing breast, thyroid, and endometrial cancer. BRR is characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis. PS includes hamartomatous overgrowth of multiple tissues as well as nevi of the connective tissue and epidermis. Proteus-like syndrome refers to individuals with features of PS, but who do not meet diagnostic criteria.
PHTS is inherited in an autosomal dominant manner. Approximately 85% of individuals meeting diagnostic criteria for CS and 65% clinically diagnosed with BRR have a PTEN mutation. Data suggest that 50% of individuals with PS and 20% with Proteus-like syndrome have detectable mutations. Individuals with autism and macrocephaly have also been identified with PTEN mutations especially if there is a family history consistent with CS or BRR.
This analysis includes both Sanger sequencing and deletion/duplication by MLPA including the promoter region.