Download COWDEN SYNDROME (CS)

COWDEN SYNDROME (CS) Cowden Syndrome (CS) is a rare genetic condition that can be passed on throughout a family. Individuals with CS are at higher risk to develop various types of growths or tumors. Some of these tumors are benign (harmless) and others are cancerous. CS leads to an increased risk for thyroid cancer, as well as uterine and breast cancer in women. Signs and Symptoms The following can be associated with CS: • Benign and cancerous tumors (details below) • Large head size (“macrocephaly”) • Cobblestone appearance of the tongue (“papillomatous papules”) • Hard growths on the skin (“keratoses”) found on the arms, legs, palms of the hands, or soles of the feet • Flesh colored, flat‐topped, dry, or warty papules around the mouth, nostrils, or eyes (“trichilemmomas”) • Developmental delay/mental retardation (15‐20% of people with CS) It is important to note that CS affects each individual differently, even those from within the same family. Most people have some, but not all, of these symptoms. Cancer Risks Cancer Type Lifetime Risk in Average Risk Comments CS Breast (Female) 30‐50% 12% Typical age of diagnosis is between age 38 and 46. Uterine/endometrial 5‐10% 2‐3% (Female) Thyroid 3‐10% Less than 1% Follicular or papillary thyroid cancer, not medullary. Skin cancer and kidney cancer (specifically, renal cell carcinoma) can also occur with CS but are much less common. 1
Benign Tumor Risks Benign Tumor Benign breast disease (Female) Goiter or thyroid adenoma Polyps in the stomach, small intestine, or colon Lipomas (benign fatty tumors) Lhermitte‐Duclos disease (LDD) Lifetime Risk in CS Up to 76% 50‐70% Comments Fibrocystic disease of the breast/fibroadenomas. These are also very common in the general population. An adenoma is a pre‐cancerous growth. 42% The specific type of GI polyp seen in CS is a “hamartoma.” 27% Unknown LDD is an adult‐onset, rare, slow‐growing brain tumor in the nerve cells of the cerebellum. It can lead to seizures, tremors, and poor coordination. Genetic Basis Mutations (alterations) in the PTEN gene cause CS. Genetic testing is available for the PTEN gene. Approximately 85% of people who appear to have Cowden Syndrome have a detectable mutation the PTEN gene. This means that 15% of the time, the person is believed to have CS but the genetic testing does not find a mutation. A mutation may, in fact, be there but the current testing technology cannot identify it. Genetic testing requires a blood or saliva sample. Many insurance companies will cover testing when appropriate. Inheritance If someone has CS, their children, siblings, and parents are each at 50% risk to also have CS. If genetic testing identifies a mutation in the PTEN gene, then relatives can be tested to determine whether they also have the same gene mutation. More distant relatives (aunts/uncles, grandparents, cousins, etc…) are also at‐risk to have CS. It is important to share genetic test results with family members. If someone does not inherit a PTEN gene mutation, then they cannot pass CS onto their children. Diagnosis There are two ways to diagnose CS. Patients may fall into one or both categories. 1. Clinical diagnosis ‐ The patient’s signs and symptoms are compared to definite clinical criteria. If a patient meets the clinical criteria, he/she has a diagnosis of CS. 2. Genetic testing ‐ The patient’s DNA is examined for mutations in the PTEN gene. If a mutation in the PTEN gene is identified, the patient has a diagnosis of CS. 2
Cancer Risk Reduction and Prevention Cancer is the primary health risk for patients with CS. Thus, it is important to screen these individuals carefully for specific cancers. This will help to ensure that cancers are detected at their earliest, most treatable stages. The National Comprehensive Cancer Network (www.nccn.org) recommends the following for individuals with germline PTEN mutations, as well as those who have a clinical diagnosis of CS: Type of How often? Age to begin Surveillance Physical Annual 18 (or 5 years prior to earliest diagnosis of a CS‐related cancer in the family) examination Breast Self Monthly 18 Examination Clinical Breast Twice a year 25 (or 5‐10 years prior to earliest case of breast cancer in the family) Examination Mammography and Annual Age 30‐35 (or 5‐10 years prior to earliest case of breast cancer in family)
breast MRI screening Thyroid Annual Age 18 examination by palpation and ultrasound Other Considerations: 1. Risk‐reducing mastectomy and hysterectomy on case‐by‐case basis. 2. Annual dermatologic examination. 3. Education about symptoms of endometrial cancer and participation in clinical trials to determine effectiveness of screening modalities. 4. Colonoscopy with endoscopy at age 30, however, there is no formal guideline for gastrointestinal examination as research suggests that hamartomatous polyps are unlikely to become cancerous. 5. If a relative has had kidney cancer, consider screening for kidney cancer. Resources University of Iowa Hospitals and Clinics Cowden Syndrome: A guide for patients and their families http://www.uihealthcare.com/topics/medicaldepartments/cancercenter/cowden/index.html National Society of Genetic Counselors Allows individuals to locate a cancer genetic counselor in their local area. www.nsgc.org 3