{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:09:52Z","timestamp":1792393792421,"version":"4.4.0"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan\u2013Riley\u2013Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K\/AKT\/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.<\/jats:p>","DOI":"10.3390\/medicina60050767","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T15:09:36Z","timestamp":1715008176000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0975-5200","authenticated-orcid":false,"given":"Lorin-Manuel","family":"P\u00eerlog","sequence":"first","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrada-Adelaida","family":"P\u0103tr\u0103\u0219canu","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela Sanda","family":"Militaru","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"},{"name":"Regional Laboratory Cluj-Napoca, Department of Medical Genetics, Regina Maria Health Network, 400363 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"C\u0103tan\u0103","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d, 400012 Cluj-Napoca, Romania"},{"name":"Regional Laboratory Cluj-Napoca, Department of Medical Genetics, Regina Maria Health Network, 400363 Cluj-Napoca, Romania"},{"name":"Department of Oncogenetics, \u201cProf. Dr. I. Chiricu\u021b\u0103\u201d Institute of Oncology, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104533","DOI":"10.1016\/j.ejmg.2022.104533","article-title":"Catch Them If You Are Aware: PTEN Postzygotic Mosaicism in Clinically Suspicious Patients with PTEN Hamartoma Tumour Syndrome and Literature Review","volume":"65","author":"Hendricks","year":"2022","journal-title":"Eur. J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-med-052218-125823","article-title":"The Clinical Spectrum of PTEN Mutations","volume":"71","author":"Yehia","year":"2020","journal-title":"Annu. Rev. 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