Clinical Guidance

For purposes of PTEN genotype-phenotype analyses, a series of 37 unrelated probands with CS were ascertained by the operational diagnostic criteria of the International Cowden Consortium, 1995 version . Association analyses revealed that families with CS and a germline PTEN pathogenic variant are more likely to develop malignant breast disease than are families who do not have a PTEN pathogenic variant . In addition, pathogenic missense variants and others 5' to or within the phosphatase core motif appeared to be associated with involvement of five or more organs, a surrogate phenotype for severity of disease . More than 90% of families that included individuals with CS and also individuals with BRRS were found to have a germline PTEN pathogenic variant.

Diagnostic Criteria

Suggestive Findings

The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. PTEN hamartoma tumor syndrome (PHTS) should be suspected in individuals with the following clinical features.

Cowden Syndrome (CS)

Based on more than 3,000 prospectively accrued cases of CS or Cowden-like syndrome (CLS) from the community, a scoring system (which can be found online) that takes into account phenotype and age at diagnosis has been developed. The scoring system allows input of clinical information on an individual suspected of having CS/CLS and subsequently generates the prior probability of finding a PTEN pathogenic variant.

Management Guidelines

Evaluations and Surveillance Guidelines Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with PTEN hamartoma tumor syndrome (PHTS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. The most serious consequences of PHTS relate to the increased risk of cancers including breast, thyroid, endometrial, renal, and to a lesser extent, colon. In this regard, the most important aspect of management of any individual with a PTEN pathogenic variant is increased cancer surveillance to detect any tumors at the earliest, most treatable stages. Current suggested screening and surveillance by age are detailed in .