WebBirtHoggDub syndrome (BHD), also HornsteinBirtHoggDub syndrome, HornsteinKnickenberg syndrome, and fibrofolliculomas with trichodiscomas and acrochordons is a human, adult onset, autosomal dominant genetic disorder caused by the FLCN gene. Kim Taylor is an editor with Healthgrades working to positively impact the lives of others through empathetic and meaningful content. The earliest case of possible BHD in the medical literature was published by Burnier and Rejsek in 1927,[22] who described a case of perifollicular fibromas on a 56-year-old woman's face. If you have questions about MD Andersons appointment process, our information page may be the best place to start. Cleveland Clinic is a non-profit academic medical center. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to the formation of noncancerous and cancerous tumors. 2019 Feb 1;129(2):452-464. doi: Lynch syndrome is a condition that increases the risk of many kinds of cancer. People with PHTS can develop characteristics associated with both Cowden syndrome and BRRS over their lifetimes. Thomas removed the lump and diagnosed it as a dermatofibrosarcomaprotuberans, a rare cancer that develops in the deep layers of skin. 2009 Jaundice is a lifelong finding, but the disease is not associated with morbidity or mortality, and life expectancy is not affected. In general, healthcare providers may suspect Cowden syndrome if you have a combination of specific symptoms. Doctors may treat skin lesions with: Other treatments will depend on the presence of any cancers or structural irregularities. Other cancers linked to Cowden syndrome include: PTEN hamartoma tumor syndrome (PHTS) is a group of inherited syndromes that involve genetic changes (mutations) to the PTEN gene. Advertising on our site helps support our mission. WebAlthough initially not regarded as being part of the syndrome, breast cancer has long been recognized as the most common CS malignancy. Cowden syndrome is a rare genetic (inherited) condition. Recent [7] Hybrid oncocytoma/chromophobe carcinoma, found in 50% of cases,[8] is the most commonly found cancer, followed by chromophobe renal carcinoma, clear cell renal carcinoma, renal oncocytoma, and papillary renal cell carcinoma. The drug was being tested for its ability to block the growth of cancer cells in people with Cowden syndrome. With nothing to lose, Jon opted for the clinical trial. For the next eight months, his life revolved around the clinical trial. CS is a relatively rare inherited condition. You may also be at increased risk of developing malignant (cancerous) tumors. [2] These tumors often occur in both kidneys and in multiple locations in each kidney. In early CS, many people begin to experience symptoms involving their skin and mucous membranes. People with Cowden syndrome have a mutation in the PTEN gene. WebNCI's Dictionary of Cancer Terms provides easy-to-understand definitions for words and phrases related to cancer and medicine. The only known risk factor for Cowden syndrome is a family history of the condition. Heterozygotes have renal abnormalities seen very early in life that develop into clear-cell and hybrid tumors, significantly shortening the animals' lifespans; they also are prone to endometrial and salivary gland clear-cell hyperplasia as well as rhabdomyolysis. It can cause susceptibility to kidney cancer, renal and pulmonary cysts, and Before his thyroid surgery, Jons lungs had been X-rayed a common, pre-operative requirement. Clin Cancer Res. The Lyda Hill Cancer Prevention Center provides cancer risk assessment, screening and diagnostic services. Four-time cancer survivor spreads awareness of Cowden syndrome, Physician Relations Continuing Education Program, Specialized Programs of Research Excellence (SPORE) Grants, Prevention & Personalized Risk Assessment, MD Anderson UTHealth Houston Graduate School, Comparative Effectiveness Training (CERTaIN), Cancer Survivorship Professional Education, Post Graduate Fellowship in Oncology Nursing, Argyros Postdoctoral Research Fellowship in Oncology Nursing, Professional Student Nurse Extern Programs, MD Anderson UTHealth Graduate School of Biomedical Sciences. [6] FLCN has been found to be overexpressed in fibrofolliculoma tissue, and to have very low levels of expression in affected kidneys. Epub 2018 May 23. According to experts, at least 40% of people with CS will experience at least one type of cancer. MedlinePlus also links to health information from non-government Web sites. Copyright 2023 Healthgrades Marketplace, LLC, Patent US Nos. This is why cancer screenings are so important. [8] The C-terminal end of folliculin has shown to be the domain through which it interacts with FNIP1, and thereby possibly the mTOR pathway. [6], The different manifestations of BHD are controlled in different ways. [5], People over 20 years of age with BHD have an increased risk of developing slow-growing kidney tumors (chromophobe renal carcinoma and renal oncocytoma, respectively), kidney cysts, and possibly tumors in other organs and tissues. Most affected people also have characteristic dark blue to dark brown macules around the mouth, eyes, and nostrils; near Doctors offered Jon two treatment options. While showering one morning, he discovered a curious, hard lump on his back. That means they inherit one copy of the gene from each biological parent and have a 50% chance of inheriting the mutated gene. More research is needed to understand the cancer risks of BRRS. [16], FLCN creates a protein, folliculin, that has two isoforms. Epub 2008 Sep 10. Both Cowden syndrome and Cowden-like syndrome are caused by mutations in the same genes. [18], BHD can be suggested by clinical findings but is definitively diagnosed by molecular genetic testing to detect mutations in the FLCN gene. [7], Renal cystogenesis and tumorigenesis in BHD have been shown to be driven by the constitutive activation of TFEB. Eng C, Pandolfi PP. About 25 percent of Cowden syndrome and a small percentage of cases of Cowden-like syndrome result from mutations in the PTEN gene. He refused. [6], In general, people with this syndrome are at roughly at seven times the risk of kidney cancer compared to the unaffected population. A biopsied trichilemmoma, meaning tissue samples studied under a microscope show signs of trichilemmoma. Waite KA, Eng C. Germline mutations and variants in the succinate dehydrogenase [14] Less severe skin phenotypes are seen in women and people of both sexes who have a late onset of skin symptoms.[5]. Change the lives of cancer patients by giving your time and talent. The fibrofolliculomas can be removed surgically, through curettage, shave excision, skin resurfacing, or laser ablation; this is not a permanent solution, though, as the tumors often recur. This article discusses the causes, symptoms, diagnosis, and treatments for Cowden syndrome. Hamartomas (pronounced HA-mar-TOH-muhs) are among the obvious and most common signs of Cowden syndrome. PHTS can lead to benign tumors and skin growths, and can increase your cancer risk. This gene provides instructions for making a protein called killin. Learn about clinical trials at MD Anderson and search our database for open studies. Its also important to know the potential warning signs of cancer. Still, careful screening can potentially save or prolong your life if you develop cancer. If you have Cowden syndrome, youre at greater risk than the general population for certain cancers. Kidney tumors, both cancerous and benign, occur in 1434% of people with BHD; the associated kidney cancers are often rare hybrid tumors. However, early checkups can help doctors detect any cancers early and provide prompt treatment. Request an appointment online or by calling 1-877-632-6789. Doctors once viewed Cowden syndrome and BRRS as separate conditions. No. BirtHoggDub syndrome affects the skin and increases the risk of tumors in the kidneys and lungs. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. http://www.ncbi.nlm.nih.gov/books/NBK1488/. [6] Cause They may also have an increased risk of developing certain cancers. The goal is to catch it early, then force it to back down.. Will I develop other kinds of cancer? WebCowden syndrome. To diagnose Cowden syndrome, healthcare providers compare your situation with diagnostic criteria developed by medical professionals who specialize in genetic (inherited) cancer syndromes. [14][3] Very rarely, missense mutations are observed. A Cowden syndrome diagnosis means you have a specific combination of conditions. Cancer No. 15;21(2):300-10. doi: 10.1093/hmg/ddr459. We do not endorse non-Cleveland Clinic products or services. [5], Birt, Hogg, and Dub examined a family with a hereditary thyroid cancer, and discovered that many of the members had fibrofolliculomas, trichodiscomas, and acrochordons, which became defined as the classical symptoms of the eponymous disease. 10.1001/jama.2010.1877. People with PHTS and BRRS face similar health risks. Sherman ordered a tissue sample from the suspicious spot on Jons lung. In this case, people inherit a normal gene from one biological parent and a mutated gene from the other biological parent. Cowden syndrome (also known as Cowden's disease and multiple hamartoma syndrome) is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, and other cancers. It heats the tumor and destroys the cancer cells. Screening procedures may include frequent: Depending on the results, you may need a biopsy to determine if abnormal tissue contains cancer cells. GeneReviews(R) [Internet]. These lesions are usually found in the armpit, on the eyelids, and in folds of skin. [15] These mutations are often passed from one generation to the next in an autosomal dominant fashion, but can occur as a new mutation in an individual with no prior family history (a de novo mutation). Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. MERRF = myoclonus, epilelpsy and ragged-red fibers. The overgrowth is usually asymmetric, which means it affects the right and left sides of the body differently. [5] Tuberous sclerosis must be distinguished because both disorders can present with angiofibromas on the face, though they are more common in tuberous sclerosis. Normally, the gene makes a protein that helps control the rate at which cells divide and grow. Colonoscopies should be considered. It turns out thyroid cancer had not spread to his lung, after all. SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like It also causes multiple noncancerous, tumor-like growths that resemble skin tags, goosebumps or razor burn on various parts of the body. In some cases, such as when genetic tests dont find PTEN mutations, you may need several kinds of tests so your providers can rule out other conditions. PTEN germline mutation? Ask your healthcare provider about your health risks if youre diagnosed with PHTS. Log in to our secure, personalized website to manage your care (formerly myMDAnderson). For the next eight months, his life revolved around the clinical trial. If Id known the extent of your disease, the doctor told Jon, I would have sent you to MD Anderson the minute you walked through my door. A person can also receive a diagnosis of CS if they have one major and three minor criteria. Fibrofolliculomas are the most common manifestation, found on the face and upper trunk in over 80% of people with BHD over the age of 40. Pulmonary cysts are equally common (84%), but only 24% of people with BHD eventually experience a collapsed lung (spontaneous pneumothorax). It makes an enzyme that prevents uncontrolled cell growth that causes tumors. We want them to see us, he says, not just read about us in a book.. In other cases, the genetic changes associated with CS happen spontaneously during a persons life. [3] It appears to act as a tumor suppressor, and is expressed strongly in the skin, distal nephrons, and type I pneumocytes. In some instances, you dont inherit a mutated PTEN gene. [3] The tumors are always found on and around the nose and on and behind the outer ear. Hum Mol Genet. Regular checkups are essential to identifying and managing complications and improving outcomes. Epub 2019 Jan 7. 10.1172/JCI121277. The average age of Blood vessel growths that appear through your skin (, Polyps in your upper gastrointestinal tract and colon (. WebSymptoms of the disease most commonly manifest in the third and fourth decades of life, although it may onset at any age. When you have a rare disease, you have an obligation to give back, he says. Youre at increased risk of developing certain types of cancer if you have PHTS/Cowden syndrome. Why is this happening to me?. Dermatologic examinations, neck ultrasounds and colonoscopies should be considered as well [1]. Endocr Relat Additionally, the International Cowden Consortium has developed criteria for diagnosing Cowden syndrome. MD Anderson is your best hope., Days later, Jon arrived in Houston and embarked on what he calls an epic cancer saga I never could have anticipated in my wildest dreams.. BHD-associated tumorigenesis differs between the kidney, where loss of FLCN heterozygosity is responsible for cancers, and the skin, where FLCN is strongly expressed in heterozygotes. Men, especially those with Cowden syndrome, can develop breast cancer, Jon explains. Learning of a PHTS diagnosis can be difficult, whether the diagnosis applies to you or your child. These conditions are differentiated from BHD through examining the patient history and performing a physical examination. To use the sharing features on this page, please enable JavaScript. Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer At a follow-up appointment one week after surgery, Jon learned he had follicular thyroid cancer an aggressive form of the disease and it had invaded his blood and lymph vessels. The disease was discovered in 1977, but the connection with FLCN was not elucidated until 2002, after kidney cancer, collapsed lungs, and pulmonary cysts were all definitively connected to BHD. See our, URL of this page: https://medlineplus.gov/genetics/condition/cowden-syndrome/. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. Third Party materials included herein protected under copyright law. Youll need lifelong cancer screening to manage the risk. CS can be manageable with regular screenings and prompt treatment. Screening cant prevent cancer, but early detection can lead to early treatment and better outcomes. The genitals may also be affected. The condition is characterized by multiple noncancerous, dome-shaped tumors of the hair follicles (fibrofolliculomas), particularly on the face, neck, and more rarely, the upper chest. Your gift will help support our mission to end cancer and make a difference in the lives of our patients. 2012 Jan Genet Med. Spreading awareness about Cowden syndrome. THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. Cowden syndrome happens when you inherit certain genetic mutations. Submission of this form is subject to Healthgrades, Help Millions of people find the right doctor and care they need, Get immediate care and visit with providers from the comfort of your home, or anywhere, Urgent care centers can be faster and cheaper for situations that are not life threatening, Doctors and patients discuss the latest medical treatments and health tips, Search prescription drugs for why theyre used, side effects and more, Back and Neck Surgery (Except Spinal Fusion), View All Symptoms and Conditions Articles, https://medlineplus.gov/genetics/condition/cowden-syndrome/, https://rarediseases.info.nih.gov/diseases/6202/cowden-syndrome, https://www.ncbi.nlm.nih.gov/books/NBK525984/, https://dermnetnz.org/topics/cowden-disease, https://www.frontiersin.org/articles/10.3389/fmed.2021.658842/full, macrocephaly, or a larger-than-usual head, irregularities in the blood or lymphatic vessels. After consulting Jons medical team, urologist Christopher Wood, M.D., used radiofrequency ablation to destroy the tumor with heat. Policy. You may develop cancer at an early age and you may have more than one kind of cancer at different times in your life. If you have PHTS, youre at increased risk of developing hamartomas and other benign growths. Cowden syndrome is rare. With nothing to lose, Jon opted for the clinical trial. [2] The BHD Foundation supports research into the syndrome and holds regular symposia in BHD and related disorders for researchers, clinicians, and family members. syndrome via FAD/NAD-dependant destabilization of p53. Your healthcare provider will diagnose you with PHTS if they find a mutation in the PTEN gene. [11], Thyroid nodules[2] have been associated with the BirtHoggDub phenotype, present in 65% of individuals and 90% of families with the syndrome. Multiple lipomas, GI hamartomatous polyps, trichilemmomas. A relative who has Cowden syndrome or related conditions like. A large number of tumors on the face can be associated with hyperseborrhea (abnormally elevated sebum production). 2018 Aug;25(8):T121-T140. Theyll move quickly to treat cancer before it spreads. [5] In women suspected to have the disease, ruling out pulmonary or thoracic endometriosis may be necessary. Your outlook depends on many factors, including your symptoms and overall health. Oncogene. People with this condition have problems with the skin, head and face, inner ear, and heart. Our personalized portal helps you refer your patients and communicate with their MD Anderson care team. This means that some people with the clinical diagnosis have mutations that are not detectable by current technology, or that mutations in another currently unknown gene could be responsible for a minority of cases. Thats why people with Cowden syndrome are at increased risk of developing multiple cancers before the age of 50, including thyroid, breast, uterine, colorectal, kidney, lung and skin cancer. Like the protein produced from the PTEN gene, killin probably acts as a tumor suppressor. It is considered to be under-diagnosed[3][6] because of the variability in its expression. I needed another option, and I needed it fast, he says. People with Cowden syndrome often have many noncancerous, tumor-like growths. The PTEN gene likely has other important functions within cells; however, research is needed to determine what role mutations in this gene play in causing the other features of Cowden syndrome, such as macrocephaly and intellectual disability. PTEN is a tumor suppressor gene. WebPTEN mutation analysis identified a deletion in exon 2, confirming the diagnosis of Cowden syndrome. Am J Hum Genet. Learn about our graduate medical education residency and fellowship opportunities. [3] Not all individuals develop the facial tumors; some families with the mutation that causes BHD develop only kidney tumors or spontaneous pneumothorax. Bennett KL, Mester J, Eng C. Germline epigenetic regulation of KILLIN in Follow your healthcare providers guidance on whether and how often you should be screened. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Theyll need frequent cancer screening tests that may detect cancer before it causes symptoms. Shes helped me through several procedures, he says. Coming to a Cleveland Clinic location?Hillcrest Cancer Center check-in changesCole Eye entrance closingVisitation and COVID-19 information, Notice of Intelligent Business Solutions data eventLearn more. Some people do not meet the strict criteria for a clinical diagnosis of Cowden syndrome, but they have some of the characteristic features of the condition, particularly the cancers. Talk with your healthcare provider about the timing and frequency with which youll need cancer screening. Ask your healthcare provider about any symptoms that you should be on the lookout for. People with Cowden syndrome often have many noncancerous, tumor-like growths and skin issues. Cells can grow out of control when theres a mutation, causing hamartomas. Jon underwent a four-hour surgery to remove the invasive tumor, along with his entire thyroid gland. Ni Y, Zbuk KM, Sadler T, Patocs A, Lobo G, Edelman E, Platzer P, Orloff MS, What are the odds of having two, unrelated, back-to-back cancers? Jon recalls thinking. The resulting image revealed a curious shadow on his lower left lung. The major criteria include: To receive a diagnosis of Cowden syndrome, a person must have two of the major criteria. One of these criteria must be either Lhermitte-Duclos disease or macrocephaly. A person can also receive a diagnosis of CS if they have one major and three minor criteria. The process involves comparing your situation with major and minor criteria. Our patients depend on blood and platelet donations. Either white or mucosa-colored, they are discrete, small, and soft, and consist of fibrous tissue covered in thickened epithelium. He tries to maintain as much normalcy as possible. Most people are in their 20s before they notice changes in their body that may be Cowden syndrome signs and symptoms. Some people with Cowden syndrome have relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other affected individuals have the characteristic features of both conditions. (https://www.dovepress.com/genetic-basis-of-cowden-syndrome-and-its-implications-for-clinical-pra-peer-reviewed-fulltext-article-TACG), (https://ghr.nlm.nih.gov/condition/cowden-syndrome), (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222536/). [5] Men and women are equally affected, and there is This means that only one parent has to pass down a copy of a mutated gene for their child to have the condition. But there are a few things you should avoid doing. The outlook for people with CS can be positive. This loss of heterozygosity is a common mechanism in cancer, and it is frequently detected in the renal cancers associated with BHD. A CT scan ordered by a Dallas doctor revealed why. 2008 Nov;16(11):1289-300. doi: 10.1038/ejhg.2008.162. 2001 Nov 29 [updated Experts estimate that it affects about one in 200,000 people, but that number might In the remaining cases, the genetic cause is unknown. With PHTS, the PTEN gene doesnt work correctly. of Washington, Seattle; 1993-2023. How are genetic conditions treated or managed? The medicine eventually made Jon so nauseated that doctors were ready to downgrade his dosage. (https://pubmed.ncbi.nlm.nih.gov/32568377/), (https://pubmed.ncbi.nlm.nih.gov/31433956/), Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline, (https://pubmed.ncbi.nlm.nih.gov/29684080/). What are some potential complications of Cowden Yehia L, Ni Y, Sesock K, Niazi F, Fletcher B, Chen HJL, LaFramboise T, Eng C. Recent studies suggest that folliculin accomplishes this function through its involvement with cellular metabolism, possibly through modulation of the mTOR (mammalian target of rapamycin) pathway and/or oxidative phosphorylation in mitochondria. A characteristic symptom of CS is the development of multiple hamartomas in different areas of the body. Talk with your care team about setting up a screening schedule. Cowden syndrome is a rare genetic (inherited) condition. Treatments may include: If you have Cowden syndrome, youll need lifelong surveillance to monitor for benign and cancerous growths to detect any issues at the earliest, most treatable time.