Cowden syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at June 25, 2016
StartDiseasesCowden syndrome

Cowden syndrome (CS) is also known as Cowden disease or PTEN hamartoma syndrome. It is a condition that increases the risk of non-cancerous tumors referred to as benign as well as certain types of cancers. Other syndromes clinically prove to be linked to PTEN hamartoma are proteus syndrome and Bannayan-Riley-Ruvalcaba syndrome

Contents

Definition & Facts

Cowden syndrome is a rare inherited disorder characterized by multiple non-cancerous, tumor-like growths widely known as hamartomas. The tumor-like growths are mostly found on the mucous membranes and the skin. However, they can also occur in other parts of the body such as the intestines.

The growth of these tumors becomes more apparent when the individual is in their late twenties. 90% of CS cases present symptoms by the time the individual is in his or her late twenties. CS greatly increases the risk of cancerous tumors of the kidney, breast, endometrium, and colon. It also increases the risk of melanoma. Other diseases of the thyroid, breast, and endometrium are often common among people with CS. CS was first described in 1963 and was named after a young woman Rachel Cowden who had the features of the syndrome.

Symptoms & Complaints

The syndrome has different symptoms that can occur at varying times depending on the person. The individual may notice skin changes such as skin tags (trichilemmomas) and papillomatous papules, for example. The most common features of CS are tiny wart-like growths that may appear on the hands, mouth or the face. There is also consistency in the growth of small bumps on the skin usually around the hair follicles.

They may also have a larger-than-average-sized head (macrocephaly) and Lhermitte-Duclos disease (non-cancerous brain tumor). Affected people may experience a developmental delays or struggle with intellectual disability. Rarely, growths of the blood vessels (hemangiomas) or benign fatty tumors can be seen. Goiter and thyroid adenomas may also be features of CS.

Women have especially been reported to be at greater risk of breast conditions such as fibrocystic breast disease and ductal hyperplasia. Women are advised to be aware of possible symptoms of uterine cancer such as pelvic pain, abnormal vaginal bleeding, painful urination, and painful intercourse

Causes

Cowden syndrome is linked to another disorder known as Bannayan-Riley-Ruvalcaba syndrome. Individuals with that syndrome tend to develop non-cancerous tumors as well as hamartomas. 90% of people with CS have a family history of the syndrome with close relatives having had or currently having the same syndrome in the past.

Both Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome can result from alterations in the PTEN gene. This gene works as a tumor suppressor gene, meaning that it prevents the rapid growth of cells. The genetic mutations in the PTEN gene prevent the protein from regulating cell proliferation normally which leads to uncontrolled division and growth of cells and the formation of cancerous tumors.

There are other cases of CS that result from mutations of the KLLN gene. The gene is responsible for the formation of a protein referred to killin. Killin is believed to act as a tumor suppressor. A genetic process called promoter hypermethylation occurs which inhibits the production of killin. This involves many methyl group molecules getting attached to the promoter region.

There is also a small percentage of patients who tend to have variations in SDHD gene or the SDHB gene. The two genes are responsible for the instructions of forming part of an enzyme referred to as succinate dehydrogenase (SDH). SDH provides energy for the production of cells. It also signals pathways that regulate the survival of cells and proliferation.

When there are variations in the gene, the function of SDH may be altered. Studies suggest that the altered SDH enzyme may give way to the unchecked growth of cells, leading to the formation of hamartomas. When CS is not related to SDHB, KLLN, PTEN or SDHD genes, the cause is defined as unknown. 

Diagnosis & Tests

Diagnosing Cowden syndrome is complex because new information on the disease is continually being discovered, and it is under constant study. Diagnosis involves a wide range of criteria originally established by the International CS Consortium although that has been revised over time. Criteria includes the following:

Although research is still ongoing, at least 80% of people reported to have met the clinical diagnosis of CS have had a mutation in the PTEN gene. Genetic testing can be carried out through blood tests to determine if a particular patient has a mutation in the PTEN gene. 

Treatment & Therapy

Treatment of Cowden syndrome is focused on prevention. Every year, recommendations for cancer screening for CS patients are updated by the NNCN-the National Comprehensive Cancer Network. Regular screenings monitor benign growths and also detect cancer at early stages when treatment can be carried out comfortably. It is important to undergo proper examinations and appropriate radiography and laboratory tests yearly.

There are also medications recommended to reduce the risks of cancer. Such medications may include raloxifene, tamoxifen, and exemestane. It is advisable to get the recommendations from a physician. Genetic counseling for relatives of those with Cowden syndrome is necessary. Treatment for skin lesions can be done using chemical peels and shave excisions.

Prevention & Prophylaxis

Preventing Cowden syndrome means pursuing screening for the various diseases associated with it. Based on the number of colorectal polyps a person is diagnosed with, the frequency of colonoscopies could increase.

Due to the high risks of breast cancer in women, CS patients are expected to have regular screening. That includes frequent breast examinations and an annual mammogram beginning at age 30-35 years of age. Surgery may be carried out to remove breast tissue. The surgery is referred to as prophylactic mastectomy. It reduces the chances of cancer by 90% and beyond.