Introduction to Cowden Syndrome

What is/are Cowden Syndrome?

Cowden Syndrome - Methods We collected clinical data of patients with hereditary cancers, identified via genetic testing (or clinically diagnosed in cases of Cowden syndrome or Peutz–Jeghers syndrome), and treated in our gynecological department from 2012 to 2018. ^[1] BACKGROUND Cowden syndrome, is characterized by multiple hamartomas and accompanied by a germline mutation of the phosphatase and tensin homolog gene. ^[2] Although most ECs are sporadic, 2–5% tend to be familial, being associated with Lynch syndrome and Cowden syndrome. ^[3] Cowden syndrome, a hereditary cancer predisposition and overgrowth disorder, was the first Mendelian condition associated with germline PTEN mutations. ^[4] This chapter elaborates the genetic syndromes like hereditary nonpolyposis colorectal cancer (HNPCC) syndrome also known as Lynch syndrome, hereditary breast and ovarian cancer (HOBC) syndrome, Cowden syndrome, Li-Fraumeni syndrome, and Peutz-Jeghers syndrome, which are found to be responsible for majority of the hereditary gynecological malignancies. ^[5] Cowden syndrome is an autosomal dominant genetic disease with an estimated incidence of one in 200,000. ^[6] A germline mutation in the PTEN gene induces not only PTEN hamartoma tumor syndrome, including Cowden syndrome, but also macrocephaly/autism syndrome. ^[7] This is the first human interventional study in patients with Cowden syndrome that is driven by inactivation of germline PTEN gene. ^[8] In 40% of cases, the tumor is associated with Cowden syndrome, which is part of a group of genetic disorders called polypoid hamartoma complex. ^[9] The combination of follicular thyroid carcinoma (FTC) and requirement of surgery for vascular malformation brought to mind the possibility of a diagnosis of Cowden syndrome/phosphatase and tensin homologue hamartoma tumour syndrome (CS/PHTS). ^[10] Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome are representative diseases, and both have several common clinical features and differences. ^[11] Most patients with Cowden syndrome have lesions in the gastrointestinal tract, characterized by multiple polyps of various histologic types in the large bowel, polyps in the upper gastrointestinal tract, and esophageal glycogenic acanthosis. ^[12] For example, germline PTEN mutations cause a subset of Cowden syndrome, but each component cancer belonging to this syndrome can be common in the general population or other differential diagnoses. ^[13] Germline heterozygous PTEN mutations cause subsets of Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS); these subsets are characterized by high risks of breast, thyroid, and other cancers and, in one subset, autism spectrum disorder (ASD). ^[14] However, these cancers have seldom been reported in diseases associated with germline PTEN variants, such as Cowden syndrome (CS). ^[15] A solitary tumor, as well as multifocal lesions, are found either sporadically, or associated with Cowden syndrome. ^[16] Cowden syndrome (CS) is a rare genetic disease which puts patients at an increased risk of developing mucocutaneous lesion, multiple hamartomas, breast cancer, thyroid cancer, and Lhermitte–Duclos disease (LDD). ^[17] Cowden syndrome (CS) is a phosphatase and tensin homolog gene (PTEN)-associated condition characterized by multiple mucocutaneous hamartomas and an increased risk of malignancies. ^[18] Purpose Mutations in DNA mismatch repair (MMR) genes and PTEN, diagnostic of Lynch and Cowden syndromes, respectively, represent the only established inherited predisposition genes in endometrial cancer to date. ^[19] The tumors were sequenced for mutations in the TERT promoter and 22 additional cancer-related genes, interestingly; one patient was shown to carry a deleterious intronic variant in PTEN, a tumor suppressor gene coupled to thyroid tumorigenesis and Cowden syndrome. ^[20] Cowden syndrome (CS) was diagnosed. ^[21] Cowden syndrome: Pathogenic variants in the PTEN gene are associated with PTEN hamartoma tumor syndrome (PHTS) a spectrum of highly variable conditions with overlapping features including Cowden syndrome (CS) [20]. ^[22] PHTS incorporates a number of historical clinical presentations including Bannayan‐Riley‐Ruvalcaba syndrome, Cowden syndrome, and a macrocephaly‐autism/developmental delay syndrome. ^[23] Alternatively, esophageal and cutaneous findings may result from conditions that are closely associated with and potentially pathognomonic for but distinct from the underlying disease process, as in genetic diseases such as Cowden syndrome or paraneoplastic syndromes such as acrokeratosis paraneoplastica. ^[24] Cowden syndrome is a rare entity related to the PTEN gene. ^[25] Cells that lack PTEN function are radiation sensitive in cell culture-based experimental systems; therefore, patients with Cowden Syndrome (CS) may carry an increased risk for normal tissue injury after radiotherapy. ^[26] Cowden syndrome (CS) is an autosomal dominant mendelian disease related to germline pathogenic variants affecting the PTEN-gene. ^[27] CASE DESCRIPTION A 50-year-old patient with Cowden syndrome initially presented with vertigo and imbalance. ^[28] Cowden syndrome (CS) is a rare disorder characterised by multiple non-cancerous, tumour-like growths called hamartomas. ^[29] The last of these three diagnoses should prompt investigations for Cowden syndrome, but intramucosal lipomas are more often sporadic/non-syndromic. ^[30] It is also seen in conditions like neurofibromatosis type 1 and Cowden syndrome. ^[31] Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. ^[32]

multiple hamartoma syndrome

Because of the association of these two neoplasms, the possibility of Cowden Syndrome - multiple hamartoma syndrome - was raised, but was excluded by genetic analysis of PTEN gene. ^[1] Cowden syndrome (CS) is a multiple hamartoma syndrome associated with the development of various tumors, including endometrial cancer. ^[2] Cowden Syndrome, also referred to as Multiple Hamartoma Syndrome or PTEN Hamartoma Tumor syndrome (PHTS), is an autosomal dominant disorder with a broad clinical spectrum and wide degree of penetrance. ^[3] Because of the association of these two neoplasms, the possibility of Cowden Syndrome - multiple hamartoma syndrome - was raised, but was excluded by genetic analysis of PTEN gene. ^[4]

hereditary diffuse gastric

The most common hereditary cancer syndromes related to women's cancer include hereditary breast and ovarian cancer syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer. ^[1] These syndromes include Lynch syndrome, familial adenomatous polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome, Cowden syndrome, hereditary diffuse gastric cancer, and hereditary pancreatic cancer. ^[2] The most common hereditary cancer syndromes related to women's cancer include hereditary breast and ovarian cancer syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer. ^[3]

autism spectrum disorder

Germline mutation of PTEN is causally observed in Cowden syndrome (CS) and is one of the most common genetic causes of autism spectrum disorder (ASD). ^[1] Germline mutation of PTEN is causally observed in Cowden syndrome (CS) and is one of the most common, penetrant risk genes for autism spectrum disorder (ASD). ^[2]

autosomal dominant disorder

Cowden Syndrome (CS) is an autosomal dominant disorder characterized by hamartomatous growth in several organs and by an increased risk of malignancies, which makes its recognition essential to undertake risk reduction measures. ^[1] Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomatous neoplasms in a variety of tissues and is associated with germline mutations in the PTEN gene. ^[2]

Include Cowden Syndrome

These disorders include Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome, adult Lhermitte–Duclos disease, and autism spectrum disorders associated with macrocephaly. ^[1] Most notably, these include Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), and autism spectrum disorders with macrocephaly. ^[2] The associated syndromes include Cowden syndrome, familial adenomatous polyposis, Gardner syndrome, Carney complex and Werner syndrome. ^[3]