{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:48:33Z","timestamp":1755218913657,"version":"3.43.0"},"reference-count":13,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2021-0567_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To report an atypical presentation of a pathogenic <jats:italic>STK11<\/jats:italic> gene variant in siblings not fulfilling the clinical diagnostic criteria for Peutz-Jeghers Syndrome (PJS)<jats:italic>.<\/jats:italic>\n                     <jats:italic> <\/jats:italic>\n                  <\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2021-0567_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>Two siblings presented with prepubertal gynaecomastia and bilateral macro-orchidism, without mucocutaneous pigmentation or gastrointestinal symptoms. There was no family history of PJS. Sibling 1 had unilateral gynaecomastia. Sibling 2 had bilateral gynaecomastia, advanced bone age and bilateral testicular microlithiasis, not indicative of a large-cell calcifying Sertoli cell tumour. Genetics revealed a paternally inherited heterozygous pathogenic <jats:italic>STK11<\/jats:italic> variant (910C&gt;T) in both siblings. The diagnosis was confirmed following the identification of multiple intestinal polyps in their father.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2021-0567_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Prepubertal gynaecomastia and prepubertal macro-orchidism (testicular enlargement without virilisation), always warrant endocrinological investigation, with PJS being an important differential diagnosis. Children may not fulfil the clinical criteria for a diagnosis of PJS at presentation. Genetic testing and gastroenterological investigation of parents may aid diagnosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2021-0567","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T23:27:25Z","timestamp":1634858845000},"page":"131-134","source":"Crossref","is-referenced-by-count":1,"title":["An atypical presentation of a pathogenic <i>STK11<\/i> gene variant in siblings not fulfilling the clinical diagnostic criteria for Peutz-Jeghers Syndrome"],"prefix":"10.1515","volume":"35","author":[{"given":"Meera","family":"Shaunak","sequence":"first","affiliation":[{"name":"Department of Paediatric Endocrinology , University Hospital Southampton NHS Foundation Trust , Southampton , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Side","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics , University Hospital Southampton NHS Foundation Trust , Southampton , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadeem","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology , University Hospital Southampton NHS Foundation Trust , Southampton , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-6320","authenticated-orcid":false,"given":"Justin Huw","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology , University Hospital Southampton NHS Foundation Trust , Southampton , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"2025080613164389316_j_jpem-2021-0567_ref_001","doi-asserted-by":"crossref","unstructured":"Latchford, A, Cohen, S, Auth, M, Scaillon, M, Viala, J, Daniels, R, et al.. Management of Peutz-Jeghers syndrome in children and adolescents: a position paper from the ESPGHAN polyposis working group. J Pediatr Gastroenterol Nutr 2019;68:442\u201352. https:\/\/doi.org\/10.1097\/mpg.0000000000002248.","DOI":"10.1097\/MPG.0000000000002248"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_002","doi-asserted-by":"crossref","unstructured":"Ferraro, GA, Romano, T, De Francesco, F, Grandone, A, D\u2019Andrea, F, del Giudice, EM, et al.. Management of prepubertal gynecomastia in two monozygotic twins with Peutz-Jeghers syndrome: from aromatase inhibitors to subcutaneous mastectomy. Aesthetic Plast Surg 2013;37:1012\u201322. https:\/\/doi.org\/10.1007\/s00266-013-0188-z.","DOI":"10.1007\/s00266-013-0188-z"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_003","unstructured":"Zhang, L-J, Su, Z, Liu, X, Wang, L, Zhang, Q. Peutz-Jeghers syndrome with early onset of pre-adolescent gynecomastia: a predigree case report and clinical and molecular genetic analysis. Am J Transl Res 2017;9:2639\u201344."},{"key":"2025080613164389316_j_jpem-2021-0567_ref_004","doi-asserted-by":"crossref","unstructured":"Ham, S, Meachem, SJ, Choong, CS, Charles, AK, Baynam, GS, Jones, TW, et al.. Overexpression of aromatase associated with loss of heterozygosity of the STK11 gene accounts for prepubertal gynecomastia in boys with Peutz-Jeghers syndrome. J Clin Endocrinol Metabol 2013;98:E1979\u201387. https:\/\/doi.org\/10.1210\/jc.2013-2291.","DOI":"10.1210\/jc.2013-2291"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_005","doi-asserted-by":"crossref","unstructured":"Gourgari, E, Saloustros, E, Stratakis, CA. Large-cell calcifying sertoli cell tumors of the testes in pediatrics. Curr Opin Pediatr 2012;24:518\u201322. https:\/\/doi.org\/10.1097\/mop.0b013e328355a279.","DOI":"10.1097\/MOP.0b013e328355a279"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_006","doi-asserted-by":"crossref","unstructured":"Crocker, MK, Gourgari, E, Lodish, M, Stratakis, CA. Use of aromatase inhibitors in large cell calcifying sertoli cell tumors: effects on gynecomastia, growth velocity, and bone age. J Clin Endocrinol Metab 2014;99:E2673\u201380. https:\/\/doi.org\/10.1210\/jc.2014-2530.","DOI":"10.1210\/jc.2014-2530"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_007","doi-asserted-by":"crossref","unstructured":"Demirbilek, H, Bacak, G, Baran, RT, Avc\u0131, Y, Baran, A, Kele\u015f, A, et al.. Prepubertal unilateral gynecomastia: report of 2 cases. J Clin Res Pediatr Endocrinol 2014;6:250\u20133. https:\/\/doi.org\/10.4274\/jcrpe.1477.","DOI":"10.4274\/jcrpe.1477"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_008","doi-asserted-by":"crossref","unstructured":"Renes, JS, Knijnenburg, J, Chitoe-Ramawadhdoebe, S, Gille, JJP, de Bruin, C, Barge-Schaapveld, DQCM. Possible hints and pitfalls in diagnosing Peutz-Jeghers syndrome. J Pediatr Endocrinol Metab 2018;31:1381\u20136. https:\/\/doi.org\/10.1515\/jpem-2018-0265.","DOI":"10.1515\/jpem-2018-0265"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_009","doi-asserted-by":"crossref","unstructured":"Ulbright, TM, Amin, MB, Young, RH. Intratubular large cell hyalinizing sertoli cell neoplasia of the testis: a report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome. Am J Surg Pathol 2007;31:827\u201335. https:\/\/doi.org\/10.1097\/pas.0b013e3180309e33.","DOI":"10.1097\/PAS.0b013e3180309e33"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_010","doi-asserted-by":"crossref","unstructured":"Boudeau, J, Kieloch, A, Alessi, DR, Stella, A, Guanti, G, Resta, N. Functional analysis of LKB1\/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers syndrome patients. Hum Mutat 2003;21:172. https:\/\/doi.org\/10.1002\/humu.9112.","DOI":"10.1002\/humu.9112"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_011","doi-asserted-by":"crossref","unstructured":"Resta, N, Stella, A, Susca, FC, Giacomo, MD, Forleo, G, Miccolis, I, et al.. Two novel mutations and a new STK11\/LKB1 gene isoform in Peutz-Jeghers patients. Hum Mutat 2002;20:78\u20139. https:\/\/doi.org\/10.1002\/humu.9046.","DOI":"10.1002\/humu.9046"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_012","doi-asserted-by":"crossref","unstructured":"Lim, W, Hearle, N, Shah, B, Murday, V, Hodgson, S, Lucassen, A, et al.. Further observations on LKB1\/STK11 status and cancer risk in Peutz\u2013Jeghers syndrome. Br J Cancer 2003;89:308\u201313. https:\/\/doi.org\/10.1038\/sj.bjc.6601030.","DOI":"10.1038\/sj.bjc.6601030"},{"key":"2025080613164389316_j_jpem-2021-0567_ref_013","doi-asserted-by":"crossref","unstructured":"Yu-Liang, J, Zi-Ye, Z, Bai-Rong, L, Hao, W, En-Da, Y, Shou-Bin, N. 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