Condition: PTEN Hamartoma Tumor Syndrome

The PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders caused by mutations of the PTEN gene. These disorders are characterized by multiple hamartomas that can affect various areas of the body. Hamartoma is a general term for benign tumor-like malformations that can affect any area of the body. Hamartomas are composed of mature cells and tissue normally found in the affected area.

PHTS includes virtually all cases of Cowden syndrome (also known as multiple hamartoma syndrome) and a percentage of cases of Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome (i.e., those associated with mutations of the PTEN gene). For more information on Bannayan-Riley-Ruvalcaba syndrome and Proteus syndrome, see NORD?s individual reports on these disorders in the Rare Disease Database.

Cowden syndrome is a difficult to recognize, under-diagnosed genetic disorder characterized by the development of multiple, benign tumor-like malformations (hamartomas) in various areas of the body. Affected individuals also have a predisposition to developing certain cancers, especially cancer of the breast, thyroid or mucous membrane lining the uterus (endometrium). The specific symptoms of Cowden syndrome vary from case to case.

Bannayan-Riley-Ruvalcaba syndrome is characterized by an abnormally large head (macrocephaly), the development of multiple benign growths (hamartomatous polyps) in the intestines (intestinal polyposis), benign tumors just below the skin consisting of fatty tissue (lipomas), and excessive growth before and after birth. Symptoms vary from case to case.

Proteus syndrome is a rare, complex growth disorder characterized by disproportionate overgrowth of various parts of the body. Tissue of the bone, skin, central nervous system and eye and connective tissue are most often affected. The specific symptoms vary greatly from case to case.

The term Proteus-like syndrome is used to describe individuals with significant features of Proteus syndrome, but who fail to meet the specific diagnostic criteria for the disorder, for Cowden syndrome and for Bannayan-Riley-Ruvalcaba syndrome. Germline PTEN mutations have been identified in approximately 50 percent of these cases.
PHTS is inherited as an autosomal dominant trait. The symptoms vary greatly from case to case even among individuals in the same family. In fact, some families have members with Cowden syndrome and others with Bannayan-Riley-Ruvalcaba syndrome. In some cases, the symptoms of the two disorders may occur in the same individual, which is referred to as the Cowden/Bannayan-Riley-Ruvalcaba overlap syndrome. The likelihood of finding a germline PTEN mutation in overlap families is very high (>95%).