What is PTEN hamartoma tumor syndrome?
PTEN hamartoma tumor syndrome (PHTS) includes multiple diseases caused by mutations – or genetic changes – in the PTEN gene, namely Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS), with PTEN-associated Proteus syndrome (PS) and Proteus-like syndrome usually included as well. Clinically, PHTS is characterized by a large head circumference (macrocephaly), numerous polyps in the gastrointestinal tract, benign fatty tissue tumors, vascular malformations, and mental retardation / autism-related disorders. In addition, there is an increased risk with regard to numerous other diseases, such as cancers of the breast, endometrial, colon, kidney, skin, and thyroid.
How is PTEN hamartoma tumor syndrome diagnosed?
There are individual diagnostic criteria for the various diseases associated with PHTS along with findings indicative of the syndrome.
Clinical Diagnosis: Cowden Syndrome (Adults)
CS-specific Criteria:
Major Criteria
Minor Criteria
Making the Diagnosis
CS can be clinically diagnosed as soon as one of the following criteria has been met:
If there is CS in the family, the clinical diagnosis can be made as soon as one of the following criteria has been met:
Clinical Diagnosis: Cowden Syndrome (Children)
Macrocephaly and at least one of the following findings:
Clinical Diagnosis: Bannayan-Riley-Ruvalcaba Syndrome
There are no standard diagnostic criteria to date. The existence of BRRS is suspected with presentation of the following:
Clinical Diagnosis: PTEN-associated Proteus Syndrome
The existence of PS is suspected with presentation of the following:
Genetic Diagnostics
The diagnosis of “PTEN hamartoma tumor syndrome” is confirmed by detection of a mutation – or genetic change – in the PTEN gene.
What is the risk of cancer?
Cowden Syndrome (CS)
Patients with Cowden syndrome have an increased risk of benign and malignant tumors of the thyroid, breast, and endometrium. Due to the frequent occurrence of polyps in the gastrointestinal tract, there is also an increased risk of colon cancer. Kidney cancer can occur as part of CS as well.
Risk of Tumors
In addition to the increased risk of tumors, Cowden syndrome is also characterized by anomalies of the skin and mucous membranes. Nearly all patients exhibit these anomalies (trichilemmomas, papillomas, cornification disorders) around the age of 30.
What is also striking in patients with CS is the large head with a head circumference above the 97th percentile (macrocephaly) and a long, narrow head shape (dolicocephaly).
Bannayan-Riley-Ruvalcaba Syndrome (BRRS)
The risk of malignant tumors is comparable to that of Cowden syndrome. In addition, BRRS is also characterized by the following clinical signs:
PTEN-associated Proteus Syndrome
PS is associated with various tumors. In addition, it is also characterized by non-uniform, excessive growth of various tissues, with the skeleton, skin, fat, and central nervous system most commonly affected. There are generally no anomalies at birth, as the excessive growth usually does not begin until early childhood. Other typical clinical signs are diseases of the lungs, an increased risk of venous thrombosis, and lung embolisms.
What causes PTEN hamartoma tumor syndrome?
PTEN hamartoma tumor syndrome is caused by mutations – or genetic changes – in the PTEN gene. This gene encodes for the PTEN protein, which is involved in transmitting signals between the cells of our body. The activity of the PTEN protein specifically initiates cell death in certain cells, thereby controlling the proliferation of cells in our body. For this reason, the PTEN protein is classified as a tumor suppressor. Now if the PTEN gene is altered, the PTEN protein will no longer be able to function properly, resulting in uncontrolled cell proliferation and thus the development of tumors and other diseases.
PHTS can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease. It is also possible for the genetic change in the PTEN gene to occur as a spontaneous or new mutation, called a de novo mutation.
Is there a treatment?
The treatment of benign and malignant tumors associated with PHTS is no different from the treatment of similar, sporadically occurring tumors.
With Cowden syndrome, the manifestations in the skin and mucous membranes are rarely life-threatening. Therefore, the following treatment is recommended:
Surveillance Recommendations for the Early Detection of Cancer
Surveillance Recommendations
Cowden Syndrome
Bannayan-Riley-Ruvalcaba Syndrome
There are no standard surveillance recommendations for BRRS to date, which is why following the same treatment regimen as that of Cowden syndrome is advised. Moreover, special care should be taken to check for complications that may arise from polyps in the gastrointestinal tract (e.g. bleeding, intestinal obstruction).
Proteus Syndrome / Proteus-like Syndrome
There are no standard surveillance recommendations for PS to date, which is why following the same treatment regimen as that of Cowden syndrome is advised.
Self-Care and Support
What should I pay special attention to?
You should consult a doctor as soon as you notice changes in the skin, thickened cervical lymph nodes, nodules in the breast, vaginal bleeding, or intestinal bleeding. However, non-specific symptoms such as abdominal pain or muscle weakness should be noted and reported to a doctor as well. You should also see a doctor right away if you notice any other newly occurring abnormalities or symptoms, such pain in the legs.