{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T17:52:22Z","timestamp":1789235542552,"version":"build-2803163510"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"2","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cowden syndrome (CS) represents a rare autosomal dominant disorder caused by mutations in the\n                    <jats:italic>PTEN<\/jats:italic>\n                    gene located on chromosome 10q23.3. This entity belongs to the PTEN hamartoma tumor syndrome (PHTS) spectrum. The\n                    <jats:italic>PTEN<\/jats:italic>\n                    gene encodes a tumor suppressor protein crucial for regulating cell growth, survival, and apoptosis. Pathogenic mutations in\n                    <jats:italic>PTEN<\/jats:italic>\n                    result in dysregulated cell proliferation, manifesting clinically as benign and malignant growths across various tissues.\n                  <\/jats:p>\n                  <jats:p>\n                    CS is characterized by a predisposition to multiple hamartomas and an elevated risk of cancers, most notably in the skin, soft tissues, thyroid, breast, and gastrointestinal tract. In pediatric patients, macrocephaly is frequently the earliest feature, often accompanied by developmental delays and neurological deficits. This case series details the clinical evolution and multidisciplinary management of two siblings with CS and normal psychomotor development. Genetic testing identified a familial\n                    <jats:italic>PTEN<\/jats:italic>\n                    mutation, with multiple affected relatives, including the siblings\u2019 father, paternal aunt and paternal grandfather, each displaying distinct phenotype.\n                  <\/jats:p>\n                  <jats:p>This familial clustering highlights the autosomal dominant inheritance of CS and points out the critical importance of early genetic testing, vigilant surveillance, and tailored counselling for at-risk relatives. Phenotypic variability observed between members of the same family points out the difficulties in predicting transgenerational outcomes and complicates genetic counselling.<\/jats:p>","DOI":"10.2478\/bjmg-2024-0016","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T11:20:47Z","timestamp":1741260047000},"page":"95-100","source":"Crossref","is-referenced-by-count":2,"title":["Phenotypic Variability of Cowden Syndrome Within a Single Family: Impact on Diagnosis, Management and Genetic Counselling"],"prefix":"10.2478","volume":"27","author":[{"given":"N","family":"Ilic","sequence":"first","affiliation":[{"name":"Clinical Genetics Outpatient Clinic, Mother and Child Health Care Institute of Serbia \u201cDr Vukan Cupic\u201d , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Mitrovic","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan Cupic\u201d, , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Radeta","sequence":"additional","affiliation":[{"name":"Department for the Diagnosis and Treatment of Hematological and Oncological Diseases, Mother and Child Health Care Institute of Serbia \u201cDr Vukan Cupic\u201d , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Krasi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan Cupic\u201d , Belgrade , Serbia"},{"name":"Faculty of Medicine, Department of Pediatrics, University of Belgrade , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Vukomanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan Cupic\u201d , Belgrade , Serbia"},{"name":"Faculty of Medicine, Department of Pediatrics, University of Belgrade , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Samardzija","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan Cupic\u201d, , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Vasic","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Mother and Child Health Institute of Serbia \u201cDr Vukan Cupic\u201d , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Vlahovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pediatrics, University of Belgrade , Belgrade , Serbia"},{"name":"Department of Plastic and Reconstructive Surgery, Mother and Child Health Institute of Serbia \u201cDr Vukan Cupic\u201d , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Sarajlija","sequence":"additional","affiliation":[{"name":"Clinical Genetics Outpatient Clinic, Mother and Child Health Care Institute of Serbia \u201cDr Vukan Cupic\u201d , Belgrade , Serbia"},{"name":"Faculty of Medicine, Department of Pediatrics, University of Belgrade , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"2026060423424001649_j_bjmg-2024-0016_ref_001","doi-asserted-by":"crossref","unstructured":"Gammon A, Jasperson K, Champine M. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management. Appl Clin Genet. 2016;9:83\u201392.","DOI":"10.2147\/TACG.S41947"},{"key":"2026060423424001649_j_bjmg-2024-0016_ref_002","doi-asserted-by":"crossref","unstructured":"Zeng N, Bayan JA, He L, Stiles B. The Role of PTEN in \u03b2-Cell Growth. Open Endocrinol J. 2010;4:23\u201332.","DOI":"10.2174\/1874216501004010023"},{"key":"2026060423424001649_j_bjmg-2024-0016_ref_003","doi-asserted-by":"crossref","unstructured":"Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997 May;16(1):64\u20137.","DOI":"10.1038\/ng0597-64"},{"key":"2026060423424001649_j_bjmg-2024-0016_ref_004","doi-asserted-by":"crossref","unstructured":"Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013 Nov 6;105(21):1607\u201316.","DOI":"10.1093\/jnci\/djt277"},{"key":"2026060423424001649_j_bjmg-2024-0016_ref_005","doi-asserted-by":"crossref","unstructured":"Takayama T, Muguruma N, Igarashi M, Ohsumi S, Oka S, Kakuta F, et al. Clinical Guidelines for Diagnosis and Management of Cowden Syndrome\/PTEN Hamartoma Tumor Syndrome in Children and Adults\u2500Secondary Publication. J Anus Rectum Colon. 2023 Oct 25;7(4):284\u2013300.","DOI":"10.23922\/jarc.2023-028"},{"key":"2026060423424001649_j_bjmg-2024-0016_ref_006","doi-asserted-by":"crossref","unstructured":"Rademacher S, Eickholt BJ. PTEN in Autism and Neurodevelopmental Disorders. 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