PTEN Hamartoma Tumor Syndrome-PHTS includes Cowden syndrome (CS), Bannayan-Ruvalcaba-Riley syndrome (BRRS) and Proteus syndrome, all of which manifest themselves with significant clinical overlap but they still maintain some unique features.
Cowden syndrome – ΡΤΕΝ Hamartoma Tumor Syndrome PTEN gene
Cowden-CS syndrome is characterized by an increased risk of both benign and malignant tumors of the breast, thyroid and endometrium. Patients generally have macrocephaly and almost all will develop typical muco-cutaneous lesions from the third decade of life. Also, polyposis of the gastrointestinal tract may be present, but usually without any particular symptoms. Female patients have a high rate of benign breast tumors.
Bannayan-Riley-Ruvalcaba Syndrome-BRRS is a congenital anomaly, characterized by macrocephaly, intestinal polyposis, lipomas and enlargement of the penis. Other common features may include high birth weight, mild to severe mental and developmental retardation, muscle weakness, hyperextensible joints, macrodactyly, pectus excavatum and scoliosis. Hamartomatous polyps of the digestive system are observed in ~45% of patients. The risk for various types of cancer in patients with BRRS harboring PTEN gene mutations is similar to patients with CS.
Proteus-PS syndrome is relatively rare and manifests with generalized, unilateral or localized hamartomatous tissue overgrowth. Patients exhibit unusual malignancies, such cystic adenoma of the ovary, tumors of the testicles, tumors of the central nervous system and adenomas of the parotid.
The precise diagnosis of these syndromes, which are all inherited and are manifested in an autosomal dominant manner, is usually based on the clinical symptoms, but the final accurate diagnosis requires the identification of PTEN gene mutations. Patients with inherited mutations (germline mutations) of the PTEN gene are 5-10 times more likely to develop cancer at a very young age (<30 years) compared to the general population. Besides its use for confirming the diagnosis, genetic testing for mutations of the PTEN gene is essential for accurate risk assessment for cancer and to make appropriate recommendations regarding prevention and treatment of the malignancy.
We perform DNA sequence analysis, via Next Generation Sequencing (NGS) on a Genome Analyzer – Ion Proton platform, of all exons and intron-exon junctions/splice sites and of -1200 to -750 control regions of the PTEN gene, as well as deletion/duplication analysis through MLPA (non-detectable by DNA sequencing), allowing us to detect >98% of all pathogenic mutations of the gene.