PTEN Hamartoma Tumor Syndrome
NORD gratefully acknowledges Charis Eng, MD, PhD, Chair and Director, Genomic Medicine Institute, and Director, Center for Personalized Genetic Healthcare, Cleveland Clinic; Professor and Vice Chairman, Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, and Jessica Mester, MS, LGC, Cleveland Clinic Genetic Counselor and PTEN Study Coordinator for assistance in the preparation of this report.
Synonyms of PTEN Hamartoma Tumor Syndrome
Subdivisions of PTEN Hamartoma Tumor Syndrome
- Cowden disease
- Cowden syndrome
- multiple hamartoma syndrome
- proteus-like syndrome
The PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders caused by germline 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 malformation composed of mature cells and tissue normally found in the affected area that have grown in a disorganized manner.
Individuals with a variety of clinical diagnoses who ultimately have been found to carry a germline PTEN mutation as the underlying cause are said to have PHTS. When the strictest diagnostic criteria are used, patients with a personal and family history of Cowden syndrome (CS) features have up to an 85% chance to have a PTEN mutation. Patients with features of Bannayan-Riley-Ruvalcaba syndrome (BRRS) and with features reminiscent of but not meeting diagnostic criteria for Proteus syndrome (called Proteus-like syndrome) have also been found to have an underlying PHTS diagnosis. Recently a mutation risk calculator has been developed which can estimate the risk for adults to have a PTEN mutation based on their personal history characteristics; this tool is available online at http://www.lerner.ccf.org/gmi/ccscore/
Once thought to be completely separate conditions, patients with features of CS or BRRS and an underlying PTEN mutation are unified as all having PHTS, with CS being a diagnosis traditionally given to adults and BRRS being first described in the pediatrics literature. This makes sense given that many of the characteristics first associated with CS tend to not appear until adulthood. PHTS is inherited as an autosomal dominant trait, which means it can be passed down in a 50-50 fashion. The symptoms vary greatly from patient to patient, even among individuals in the same family. For more information on Bannayan-Riley-Ruvalcaba syndrome and Proteus syndrome, see NORD's individual reports on these disorders in the Rare Disease Database.
PTEN Hamartoma Tumor Syndrome Resources
2007, 2012, 2015