Cowden syndrome and cancer
Cowden syndrome is an inherited disorder marked by the presence of multiple benign tumor-like growths known as hamartomas. While these growths are generally noncancerous, individuals with Cowden syndrome have a significantly increased risk of developing various cancers, including breast, melanoma, kidney, rectal, colon, thyroid, and uterine cancers. The condition is linked to mutations in the PTEN gene, a crucial tumor-suppressor gene responsible for regulating cell growth. The frequency of PTEN mutations in patients with Cowden syndrome varies widely, with estimates ranging from 11 to 85 percent.
Typically diagnosed by the presence of hamartomas, Cowden syndrome can also be confirmed through genetic testing for PTEN mutations. Although treatment focuses primarily on routine cancer screening rather than the removal of hamartomas, early detection through regular monitoring can lead to successful management of developing tumors. With an estimated incidence of 1 in 200,000 to 250,000 individuals, understanding and awareness of Cowden syndrome are vital for effective screening and intervention strategies.
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Cowden syndrome and cancer
ALSO KNOWN AS: Multiple hamartoma syndrome
RELATED CONDITIONS: PTEN hamartoma tumor syndrome (PHTS), Lhermitte-Duclos disease
DEFINITION: Cowden syndrome is an inherited disorder characterized by the presence of multiple tumorlike growths, termed hamartomas. Although these hamartomas are generally benign or noncancerous, individuals with hamartomas have a predisposition to the development of certain cancers.
Risk factors: Cowden syndrome is inherited in an autosomal dominant pattern and may be inherited from just one parent.
Etiology and the disease process: Cowden syndrome is linked to mutations in the PTEN gene. PTEN is a tumor-suppressor gene that normally controls cell growth and division. The mutations in PTEN may either be inherited or occur spontaneously. Researchers have discovered the percentage of patients with Cowden syndrome who have mutations in the PTEN gene varies widely. Between 11 and 85 percent of patients with Cowden syndrome may have identified mutations in the PTEN gene. Aside from a smaller percentage of Cowden syndrome or Cowden-like syndrome cases involving a change in the KLLN, SDHB, or SDHD genes, the cause of the condition in the remaining patients is still being studied.
Incidence: The incidence of Cowden syndrome is estimated at between 1 in 200,000 and 1 in 250,000 individuals.
Symptoms: The major defining symptom of Cowden syndrome is the presence of multiple hamartomas. These growths are generally small and most often occur on the skin and mucous membranes, such as the inside of the nose and mouth. However, hamartomas may also occur on the inner lining of the intestines and within other parts of the body. Also, patients with Cowden syndrome often develop noncancerous breast and thyroid diseases. Another common symptom of Cowden syndrome is macrocephaly or an enlargement of the patient’s head.
Screening and diagnosis: Cowden syndrome is typically diagnosed through recognition of the extensive hamartomas. To help confirm a diagnosis, the PTEN gene can be sequenced to identify any mutations. Genetic testing and quantitative scoring systems for hamartomas have advanced patient diagnosis.
Treatment and therapy: Hamartomas and other symptoms related to Cowden syndrome are typically not treated; however, the main recommendation is that these patients continue to be screened for the early development of cancerous lesions. Systemic retinoids and the drug rapamycin may help to control skin lesions. Clinical trials for experimental drugs related to Cowden syndrome are ongoing.
Prognosis, prevention, and outcomes: Because Cowden syndrome is often an inherited disorder, little can be done to prevent the disease. Patients with Cowden syndrome have a heightened risk of developing certain cancers. These include breast cancer, melanoma, kidney cancer, rectum cancer, colon cancer, thyroid cancer, and uterine cancer. However, with routine screening, these tumors may be diagnosed in the early stages and, therefore, often respond well to therapy.
Bibliography
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