Cowden Syndrome
PTEN hamartoma tumor syndrome (PHTS) includes the conditions Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome (BRRS) . A mutation of the PTEN gene can cause uncontrolled cell growth and increased cancer risks.
Causes of Cowden Syndrome
Everyone has two copies of the PTEN gene. People with PHTS have a mutation in one copy of their PTEN gene pair.
The copy of the gene with the mutation can be passed on to future generations.
The chance that a child of someone with PHTS would inherit the copy of the gene with the mutation is 50 percent.
The chance that he or she would not inherit the mutation is also 50 percent.
People diagnosed with Cowden syndrome should tell their family members about their diagnosis and encourage them to undergo genetic counseling.
For patients with Cowden syndrome who do not have a PTEN gene mutation, family members may need evaluation by a medical geneticist to determine if they also meet the clinical criteria for a diagnosis of Cowden syndrome.
Symptoms of Cowden Syndrome
Breast: Women with Cowden syndrome can develop benign growths of many different types in their breasts. Common findings include fibrocystic changes, fibroadenomas, papillomas and atypical ductal hyperplasia.
Uterus: Women with Cowden syndrome can also develop benign fibroid tumors of the uterus.
Thyroid: Men and women with Cowden syndrome can also develop benign thyroid growths such as a multinodular goiter and/or Hashimito’s thyroiditis, an autoimmune thyroid condition.
Intestinal: About 90 percent of patients with Cowden syndrome will develop gastrointestinal polyps, ranging from one per patient to innumerable. Polyps can occur in both the colorectum and the upper gastrointestinal tract.
Skin: The characteristic skin findings of patients with Cowden syndrome are papillomatous papules (benign, skin-colored, raised bumps), trichilemmomas (benign tumors coming from the outer cells of the hair follicle, most frequently on the head), and lipomas (benign fatty growths). Many patients develop papillomas on their gums and/or tongue, giving them a
cobblestoneappearance.Head and brain: People with Cowden syndrome also tend to have a large head size (macrocephaly) and a head shape that is especially long (dolichocephaly). Autism and developmental delay have also been observed at increased frequency in people with Cowden syndrome.
Diagnosis of Cowden Syndrome
PHTS is diagnosed when a mutation is found in the PTEN gene.
The International Cowden Consortium has developed criteria (guidelines) to establish a diagnosis of Cowden syndrome.
A Cowden syndrome evaluation should be considered for people with adult-onset Lhermitte-Duclos disease, macrocephaly plus autism/developmental delay, numerous and mixed types of gastrointestinal polyps or a combination of Cowden syndrome features, such as thyroid and uterine cancers or breast and kidney cancers.
Treatment of Cowden Syndrome
Specialized breast cancer screening - This should include breast self-examination every month beginning at age 18, breast examination by a doctor or nurse every 6 months beginning at age 25, and mammography/breast MRI once a year beginning at age 30-35 or 5-10 years earlier than the youngest breast cancer diagnosis in the family. There are men with Cowden syndrome who have developed breast cancer. Although the risk is much lower than that for women, we would recommend that the men perform monthly breast self-examination. Some women at increased risk for breast cancer consider prophylactic mastectomy (removal of the breasts to prevent cancer).
Thyroid cancer screening - For persons with PTEN mutations we recommend a baseline thyroid ultrasound at the age of diagnosis with at least yearly follow-up thereafter by an endocrine specialist.
Imaging of the kidneys every 1-2 years starting at age 40.
A baseline colonoscopy (examination of the colon and rectum with flexible lighted tube) should be done at age 35 years, or 5-10 years younger than the earliest colorectal cancer diagnosis in the family, with follow-up dependent on the number and type of polyps found. A variety of different types of hamartomatous polyps are commonly seen in the upper gastrointestinal tract and colorectum in persons with PTEN mutations. Baseline upper endoscopy may be recommended to help establish or confirm the diagnosis of Cowden syndrome. Ongoing upper endoscopic exam of the stomach and upper small bowel is based upon the findings on the baseline exam.