Cowden syndrome

Información en español Title

Other Names:

Cowden disease; CD; Cowden's disease; Cowden disease; CD; Cowden's disease; CS; Multiple hamartoma syndrome; MHAM See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Hereditary Cancer Syndromes; Congenital and Genetic Diseases; Digestive Diseases; Hereditary Cancer Syndromes; Rare Cancers; Skin Diseases See More

Summary Summary

Cowden syndrome is an inherited condition that is characterized primarily by multiple, noncancerous growths (called hamartomas) on various parts of the body. People with the syndrome usually have large head (macrocephaly), benign tumors of the hair follicle (trichilemmomas), and white papules with a smooth surface in the mouth (papillomatous papules), starting by the late 20s. It is considered part of the PTEN Hamartoma Tumor Syndrome spectrum which also includes Bannayan-Riley-Ruvalcaba syndrome and Proteus syndrome. People who have Cowden syndrome are at an increased risk of developing certain types of cancer, such as breast, thyroid, and endometrial (lining of the uterus) cancer. Most cases are caused by mutations in the PTEN gene and are inherited in an autosomal dominant manner.^[1]^[2] Management typically includes screening for associated tumors and/or prophylactic surgeries.^[3]

Last updated: 1/6/2017

Symptoms Symptoms

Cowden syndrome is characterized primarily by multiple, noncancerous growths (called hamartomas) on various parts of the body. Approximately 99% of people who have Cowden syndrome will have benign growths on the skin and/or in the mouth by the end of their 20s. A majority of people with Cowden syndrome will also develop growths (called hamartomatous polyps) along the inner lining of the gastrointestinal tract.^[1]^[2]

People affected by Cowden syndrome also have an increased risk of developing certain types of cancer. Breast, thyroid, and endometrial (the lining of the uterus) cancers are among the most commonly reported tumors. The lifetime risk of developing breast cancer is 85%; for thyroid cancer the risk is approximately 35%; and the risk for endometrial cancer is about 28%.^[1] Other associated cancers include colorectal cancer, kidney cancer, and melanoma. People with Cowden syndrome often develop cancers at earlier ages (before age 50) than people without a hereditary predisposition to cancer.^[3]^[1]^[4]

Other signs and symptoms of Cowden syndrome may include benign diseases of the breast, thyroid, and endometrium; a rare, noncancerous brain tumor called Lhermitte-Duclos disease; an enlarged head (macrocephaly); autism spectrum disorder; intellectual disability; and vascular (the body's network of blood vessels) abnormalities.^[3]^[1]

Last updated: 1/6/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Breast carcinoma	Very frequent (present in 80%-99% of cases)
Colorectal polyposis	Very frequent (present in 80%-99% of cases)
Conjunctival hamartoma	Very frequent (present in 80%-99% of cases)
Generalized hyperkeratosis	Very frequent (present in 80%-99% of cases)
Goiter	Very frequent (present in 80%-99% of cases)
Macule	Very frequent (present in 80%-99% of cases)
Palmoplantar keratoderma	Very frequent (present in 80%-99% of cases)
Papilloma	Very frequent (present in 80%-99% of cases)
Papule	Very frequent (present in 80%-99% of cases)
Abnormality of the penis	Frequent (present in 30%-79% of cases)
Adenoma sebaceum	Frequent (present in 30%-79% of cases)
Ataxia	Frequent (present in 30%-79% of cases)
Cavernous hemangioma	Frequent (present in 30%-79% of cases)
Cognitive impairment	Frequent (present in 30%-79% of cases)
Furrowed tongue	Frequent (present in 30%-79% of cases)
Hamartomatous polyposis	Frequent (present in 30%-79% of cases)
Intellectual disability	Frequent (present in 30%-79% of cases)
Lipoma	Frequent (present in 30%-79% of cases)
Macrocephaly	Frequent (present in 30%-79% of cases)
Melanocytic nevus	Frequent (present in 30%-79% of cases)
Meningioma	Frequent (present in 30%-79% of cases)
Mucosal telangiectasiae	Frequent (present in 30%-79% of cases)
Subcutaneous nodule	Frequent (present in 30%-79% of cases)
Autism	Occasional (present in 5%-29% of cases)
Bone cyst	Occasional (present in 5%-29% of cases)
Brachydactyly	Occasional (present in 5%-29% of cases)
Cataract	Occasional (present in 5%-29% of cases)
Cellular immunodeficiency	Occasional (present in 5%-29% of cases)
Endometrial carcinoma	Occasional (present in 5%-29% of cases)
Enlarged polycystic ovaries	Occasional (present in 5%-29% of cases)
Failure to thrive	Occasional (present in 5%-29% of cases)
Follicular thyroid carcinoma	Occasional (present in 5%-29% of cases)
Gynecomastia	Occasional (present in 5%-29% of cases)
Hearing impairment	Occasional (present in 5%-29% of cases)
High palate	Occasional (present in 5%-29% of cases)
Hypopigmented skin patches	Occasional (present in 5%-29% of cases)
Increased intracranial pressure	Occasional (present in 5%-29% of cases)
Kyphosis	Occasional (present in 5%-29% of cases)
Melanoma	Occasional (present in 5%-29% of cases)
Multiple cafe-au-lait spots	Occasional (present in 5%-29% of cases)
Myopia	Occasional (present in 5%-29% of cases)
Pectus excavatum	Occasional (present in 5%-29% of cases)
Renal cell carcinoma	Occasional (present in 5%-29% of cases)
Scoliosis	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Abnormality of the vasculature	-
Adult onset	-
Angioid streaks of the retina	-
Autosomal dominant inheritance	-
Colonic diverticula	-
Fibroadenoma of the breast	-
Hydrocele testis	-
Hyperthyroidism	-
Hypoplasia of the maxilla	-
Hypothyroidism	-
Intellectual disability, mild	-
Intention tremor	-
Micrognathia	-
Narrow mouth	-
Ovarian cyst	-
Palmoplantar hyperkeratosis	-
Progressive macrocephaly	-
Skin tags	-
Subcutaneous lipoma	-
Thyroid adenoma	-
Thyroiditis	-
Transitional cell carcinoma of the bladder	-
Varicocele	-

Last updated: 9/1/2017

Cause Cause

Most cases of Cowden syndrome are caused by mutations in the PTEN gene. PTEN is a tumor suppressor gene. Mutations in PTEN result in a defective protein that is unable to carry out its normal role. This leads to the development of the various tumors and cancers associated with Cowden syndrome.^[1]

Rarely, Cowden syndrome is caused by mutations in another gene like KLLN, SDHB, SDHC, SDHD, PIK3CA or AKT1. Some affected families have no identifiable mutation in any of the genes associated with Cowden syndrome; in these families, the exact underlying cause is unknown.^[1]^[5]^[6]

Last updated: 1/6/2017

Inheritance Inheritance

Cowden syndrome is inherited in an autosomal dominant manner.^[1] This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with Cowden syndrome has a 50% chance with each pregnancy of passing along the mutated gene to his or her child.

Last updated: 1/6/2017

Diagnosis Diagnosis

A diagnosis of Cowden syndrome is based on the presence of characteristic signs and symptoms. Genetic testing for a mutation in the PTEN gene can then be ordered to confirm the diagnosis. If a mutation in PTEN is not found, genetic testing for the other genes known to cause Cowden syndrome can be considered.^[1]

The National Comprehensive Cancer Network [NCCN 2015] consensus clinical diagnostic criteria have been divided into three categories:^[4]^[1]

Pathognomonic criteria (criteria that is characteristic for a particular disease): mucosal and skin lesions
Major criteria: breast cancer, macrocephaly, thyroid cancer and endometrial cancer
Minor criteria: thyroid lesions, intellectual disability, hamartomatous intestinal polyps, fibrocystic disease of the breast, lipomas, fibromas, genital and urinary tumors or malformations, uterine fibroids

A diagnosis is given if a patient has the "pathognomonic" skin lesions, two or more major criteria, one major and 3 or more minor criteria, or 4 or more minor criteria. The diagnostic criteria for adults and children have some differences.^[4] The PTEN Cleveland Clinic Risk Calculator can be used to estimate the chance of finding a PTEN mutation in children and adults with signs and symptoms of Cowden syndrome.

Finding mutations in the PTEN gene or other causal genes confirms diagnosis.

GeneReviews offers more detailed information regarding the diagnosis of Cowden syndrome including the clinical diagnostic criteria.

Last updated: 1/6/2017

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

Because Cowden syndrome is associated with an increased risk for certain types of cancer, management is typically focused on high-risk cancer screening. According to the National Comprehensive Cancer Network 2014, the recommended screening protocol for Cowden syndrome includes:^[3]

Cancer Screening for Women

Breast self exams beginning at age 18
Clinical breast exams every 6-12 months beginning at age 25**
Annual mammogram and breast MRI beginning at age 30-35**
Annual screening for endometrial cancer with ultrasound and/or random biopsy may be considered beginning at age 30-35
Prophylactic surgeries may be considered as a preventative option for some forms of cancer

Cancer Screening for Men and Women

Annual physical examination beginning at age 18**
Annual thyroid ultrasound beginning at age 18**
Baseline colonoscopy at age 35 with follow-up every 5 years (more frequent if polyps identified)
Consider renal (kidney) ultrasound every 1-2 years beginning at age 40

**or individualized based on the earliest diagnosis of cancer in the family.

Pediatric (age <18 years)

Yearly thyroid ultrasound examination** (on identification of a PTEN pathogenic variant)
Yearly skin check with physical examination
Neurodevelopmental evaluation

If there are not any symptoms, observation alone is prudent. Cutaneous lesions should be removed only if malignancy is suspected or symptoms (e.g., pain, deformity, increased scarring) are serious. When symptomatic, topical agents (e.g., 5-fluorouracil), curettage, cryosurgery, or laser ablation may offer temporary relief. [Hildenbrand et al 2001].

GeneReviews offers more specific information on the treatment and management of Cowden syndrome.

Last updated: 1/6/2017

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Cowden syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

FORCE: Facing Our Risk of Cancer Empowered
16057 Tampa Palms Blvd. W, PMB #373
Tampa, FL 33647
Toll-free: 866-288-RISK (7475)
Fax: 954-827-2200
E-mail: info@facingourrisk.org
Website: http://www.facingourrisk.org
Hereditary Colon Cancer Foundation
1776 Park Avenue, Suite 4-203
Suite 4-203
Park City, UT 84060
Telephone: +1-334-740-8657
E-mail: info@HCCTakesGuts.org
Website: http://www.hcctakesguts.org/
PTEN Hamartoma Tumor Syndrome Foundation
E-mail: ptensyndromefoundation@gmail.com
Website: http://www.ptenfoundation.org
The National Breast Cancer Coalition/Fund
1101 17th Street Northwest
Suite 1300
Washington, DC 20036
Toll-free: 800-622-2838
Telephone: 202-296-7477
Fax: 202-265-6854
Website: http://www.stopbreastcancer.org/
The National Coalition for Cancer Survivorship
1010 Wayne Avenue
Suite 770
Silver Spring, MD 20910
Toll-free: 888-650-9127
Telephone: 301-650-9127
Fax: 301-565-9670
E-mail: info@canceradvocacy.org
Website: http://www.canceradvocacy.org
The Susan G. Komen Breast Cancer Foundation
5005 LBJ Freeway
Suite 250
Dallas, TX 75244
Toll-free: 877-465-6636
Telephone: 972-855-1600
Fax: 972-855-1605
E-mail: helpline@komen.org
Website: http://ww5.komen.org/

Social Networking Websites

PTEN World is an online discussion forum where members dealing with Cowden syndrome can share advice and support with other patients and caregivers.

Organizations Providing General Support

American Cancer Society
250 Williams Street NW
Atlanta, GA 30329
Toll-free: 800-227-2345
Website: http://www.cancer.org
CancerCare
275 Seventh Ave, Floor 22
New York, NY 10001
Toll-free: 800-813-HOPE
Fax: 212-712-8495
E-mail: info@cancercare.org
Website: http://www.cancercare.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
Genetics Home Reference (GHR) contains information on Cowden syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Cowden syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

Xeroderma Pigmentosum and other Diseases of Human Premature Aging and DNA Repair: Molecules to Patients Tuesday, September 5, 2006
Location: National Conference Center, Lansdowne, VA
Description: This meeting was a follow-up of one held in 2004. The purpose of this workshop was to gather leading scientists and clinicians in this very active area of research. The clinical and mechanistic aspects of Cowden's syndrome (CS) and related DNA repair/transcription defective disorders such as xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) were explored. Our goals were to develop new multidisciplinary collaborations, interactions, and relationships that can lead to a greater understanding of the pathophysiological mechanisms involved in these disorders and to conceive new therapeutic strategies for their treatment.

Contact: Dr. Vilhelm A. Bohr(301) 558-8223

Co-funding Institute(s): National Institute on Aging

Related Diseases Related Diseases

The following diseases are related to Cowden syndrome. If you have a question about any of these diseases, you can contact GARD.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

What types of treatments are there for Cowden syndrome? Should treatment begin right after diagnosis or is there a waiting period? See answer

Have a question? Contact a GARD Information Specialist.

References References

Eng C. PTEN Hamartoma Tumor Syndrome (PHTS). GeneReviews. 2016; http://www.ncbi.nlm.nih.gov/books/NBK1488/.
Fiala KH. Cowden Disease (Multiple Hamartoma Syndrome). Medscape Reference. 2016; http://emedicine.medscape.com/article/1093383-overview.
Daly MB & cols. Genetic/Familial High-Risk Assessment: Breast and Ovarian. National Comprehensive Cancer Network. 2015; https://www.tri-kobe.org/nccn/guideline/gynecological/english/genetic_familial.pdf.
Cowden syndrome. Orphanet. 2013; http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=243.
Ni Y, He X, Chen J, Moline J, Mester J, Orloff MS, Ringel MD, Eng C. Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53. Hum Mol Genet. January 2012; 21(2):300-310.
Orloff MS, He X, Peterson C, Chen F, Chen JL, Mester JL, Eng C. Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. Am J Hum Genet. January 2013; 92(1):76-80.