Cowden Syndrome: A Critical Review of the Clinical Literature

Department of Internal Medicine and Clinical Cancer Genetics Program, Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Ohio State University, Columbus, OH 43221, USA.
Journal of Genetic Counseling (Impact Factor: 2.24). 11/2008; 18(1):13-27. DOI: 10.1007/s10897-008-9187-7
Source: PubMed


Cowden syndrome (CS) is a multi-system disease involving hamartomatous overgrowth of tissues of all three embryonic origins and increased risks for thyroid, breast and possibly other cancers. Benign breast, thyroid, uterine and skin lesions are also common. Approximately 80% of patients with CS have an identifiable germline mutation in the PTEN gene. The majority of the existing data on the frequencies of component clinical features have been obtained from compilations of case reports in the literature, many of which predate the establishment in 1996 of consensus diagnostic criteria. Many of these reports also suffer from ascertainment bias which emphasized the dermatologic features of the disease. This paper presents an overview of Cowden syndrome focusing on a critical evaluation of the major literature on the component cancers, benign features, and molecular findings in CS, noting the limitations of the published data.

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    • "This case presentation describes two patients with Cowden Syndrome and germline PTEN mutations who were diagnosed with pulmonary neuroendocrine tumors. Both patients had the characteristic phenotype of Cowden Syn- drome [1, 2,456. Case 1 had breast cancer, macrocephaly, thyroid adenoma, and a positive family history of Cowden Syndrome. "
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    ABSTRACT: Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden Syndrome that were diagnosed with pulmonary carcinoids.
    Full-text · Conference Paper · Dec 2015
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    • "However, the characteristics of these polyps are unclear, and they are difficult to detect with conventional examination, including double-contrast X-ray study, due to the small size of the polyps and the fact that they do not protrude much [6]. These polyps have been histopathologically found to be hamartomatous or hyperplastic polyps [2]. CE allows for endoscopic imaging of the entire small bowel without discomfort [15]. "
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    ABSTRACT: Cowden syndrome is an uncommon, autosomal dominant disease characterized by multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases are reportedly complicated by malignant diseases. Hamartomatous polyps occur throughout the gastrointestinal tract, the most common sites being the stomach, colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome; however, they are difficult to detect by conventional examination, including double-contrast X-ray study. Here, we report three cases of Cowden syndrome with small bowel polyps, which were detected by capsule endoscopy. The small bowel polyps of Cowden syndrome frequently occur at the oral end of the small bowel, especially in the duodenum and jejunum, and their color is similar to that of the surrounding mucosa; additionally, the polyps are relatively small (2-5 mm). Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome.
    Full-text · Article · Jul 2015
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    • "Conversely, the presence of some features of overgrowth, including macrocephaly, is well documented in patients with PTEN mutations, and thus, the finding of a novel PTEN mutation rather than a NSD1 mutation in this patient suggests phenotypic assessment is a good, but not the best marker of the most likely causative gene. However, in this patient, there were no apparent features indicative of cancer or of mucocutaneous lesions that occur in a high prevalence among patients with Cowden syndrome [Eng, 1997; Pilarski, 2009]. PTEN may play a significant role in a number of molecular pathways regulating cellular proliferation, migration and apoptosis – all processes that are important in the regulation of normal cellular growth [Eng, 1997]. "
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    ABSTRACT: Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS. Recently, mutations and possible pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have been reported in patients with Sotos-like overgrowth features. To estimate the frequency of NSD1 defects in the Brazilian SoS population and possibly reveal other genes implicated in the etiopathogenesis of this syndrome, we collected a cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS, and analyzed the NSD1 and PTEN genes by means of multiplex ligation-dependent probe amplification and mutational screening analyses. We identified a classical NSD1 microdeletion, a novel missense mutation (p.C1593W), and 2 previously reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we identified a novel de novo PTEN gene mutation (p.D312Rfs*2) in a patient with a less severe presentation of SoS phenotype, which did not include pre- and postnatal overgrowth. For the first time, our study implies PTEN in the pathogenesis of SoS and further emphasizes the existence of ethno-geographical differences in NSD1 molecular alterations between patients with SoS from Europe/North America (70-93%) and those from South America (10-19%).
    Full-text · Article · Jan 2015 · Molecular syndromology
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