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

This disease is grouped under:

Familial breast cancer; PTEN hamartoma tumor syndrome

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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Breast carcinoma	Breast cancer	0003002
Colorectal polyposis		0200063
Conjunctival hamartoma		0100780
Generalized hyperkeratosis		0005595
Goiter		0000853
Macule	Flat, discolored area of skin	0012733
Palmoplantar keratoderma		0000982
Papilloma		0012740
Papule		0200034
30%-79% of people have these symptoms
Abnormality of the penis		0000036
Adenoma sebaceum		0009720
Ataxia		0001251
Cavernous hemangioma	Collection of dilated blood vessels that forms mass	0001048
Cognitive impairment	Abnormality of cognition Cognitive abnormality Cognitive defects Cognitive deficits Intellectual impairment Mental impairment [ more ]	0100543
Furrowed tongue	Grooved tongue	0000221
Global developmental delay		0001263
Hamartomatous polyposis		0004390
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Lipoma	Fatty lump	0012032
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Macroglossia	Abnormally large tongue Increased size of tongue Large tongue [ more ]	0000158
Melanocytic nevus	Beauty mark	0000995
Meningioma		0002858
Mucosal telangiectasiae		0100579
Subcutaneous nodule	Firm lump under the skin Growth of abnormal tissue under the skin [ more ]	0001482
5%-29% of people have these symptoms
Abnormal cerebellum morphology	Abnormality of the cerebellum Cerebellar abnormalities Cerebellar abnormality Cerebellar anomaly [ more ]	0001317
Autism		0000717
Bone cyst	Bone cysts	0012062
Brachydactyly	Short fingers or toes	0001156
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Cellular immunodeficiency		0005374
Endometrial carcinoma		0012114
Enlarged polycystic ovaries		0008675
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Follicular thyroid carcinoma		0006731
Gynecomastia	Enlarged male breast	0000771
Hearing impairment	Deafness Hearing defect [ more ]	0000365
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hypopigmented skin patches	Patchy loss of skin color	0001053
Increased intracranial pressure	Rise in pressure inside skull	0002516
Kyphosis	Hunched back Round back [ more ]	0002808
Melanoma		0002861
Multiple cafe-au-lait spots		0007565
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Pectus excavatum	Funnel chest	0000767
Renal cell carcinoma		0005584
Scoliosis	Abnormal curving of the spine	0002650
Seizures	Seizure	0001250
Short stature	Decreased body height Small stature [ more ]	0004322
1%-4% of people have these symptoms
Decreased antibody level in blood		0004313
Lymphopenia	Decreased blood lymphocyte number Low lymphocyte number [ more ]	0001888
Recurrent infections	Frequent infections Frequent, severe infections Increased frequency of infection infections, recurrent Predisposition to infections Susceptibility to infection [ more ]	0002719
Percent of people who have these symptoms is not available through HPO
Abnormality of the vasculature	Abnormality of blood vessels Vascular abnormalities [ more ]	0002597
Acrokeratosis		0200016
Adult onset	Symptoms begin in adulthood	0003581
Angioid streaks of the fundus		0001102
Autosomal dominant inheritance		0000006
Carcinoma		0030731
Colonic diverticula		0002253
Dysplastic gangliocytoma of the cerebellum		0500009
Fibroadenoma of the breast		0010619
Hydrocele testis		0000034
Hyperthyroidism	Overactive thyroid	0000836
Hypoplasia of the maxilla	Decreased size of maxilla Decreased size of upper jaw Maxillary deficiency Maxillary retrusion Small maxilla Small upper jaw Small upper jaw bones Upper jaw deficiency Upper jaw retrusion [ more ]	0000327
Hypothyroidism	Underactive thyroid	0000821
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Intention tremor		0002080
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Narrow mouth	Small mouth	0000160
Ovarian carcinoma		0025318
Ovarian cyst		0000138
Palmoplantar hyperkeratosis		0000972
Progressive macrocephaly	Progressively abnormally enlarging cranium Progressively abnormally enlarging skull [ more ]	0004481
Skin tags		0010609
Subcutaneous lipoma		0001031
Thyroid adenoma		0000854
Thyroiditis	Thyroid gland inflammation	0100646
Transitional cell carcinoma of the bladder		0006740
Varicocele		0012871

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2018

Do you have updated information on this disease? We want to hear from you.

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

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses, juvenile-polyposis syndrome, Peutz-Jeghers syndrome, Birt-Hogg-Dubé syndrome, Gorlin syndrome and neurofibromatosis type 1 (see these terms). Visit the Orphanet disease page for more information.

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 related to 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
3519 NE 15th Avenue
Unit 518
Portland, OR 97212
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: 1-800-227-2345
Website: https://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? We want to hear from you.

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

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.
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.

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. 2018; 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.