{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:55:30Z","timestamp":1793498130240,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T00:00:00Z","timestamp":1616889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303889\/2018\u20107"],"award-info":[{"award-number":["303889\/2018\u20107"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15\u00a0years (4\u201019). The median time of follow\u2010up was 145\u00a0months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation\u2010dependent probe amplification and\/or target next\u2010generation sequencing panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline <jats:italic>VHL<\/jats:italic> pathogenic variants, <jats:italic>SDHB<\/jats:italic>, <jats:italic>SDHD<\/jats:italic>, <jats:italic>RET<\/jats:italic> and negative genetic investigation, respectively. Children with germline <jats:italic>VHL<\/jats:italic> missense pathogenic variants were younger than those with <jats:italic>SDHB<\/jats:italic> or <jats:italic>SDHD<\/jats:italic> genetic defects [median (range), 12 (4\u201016) <jats:italic>vs<\/jats:italic>. 15.5 (14\u201019)\u00a0years; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.027]. Moreover, 10 of 11 cases with <jats:italic>VHL<\/jats:italic> pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline <jats:italic>SDHB<\/jats:italic> pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with <jats:italic>SDHD<\/jats:italic> pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with <jats:italic>VHL<\/jats:italic> being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14467","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T01:34:56Z","timestamp":1616290496000},"page":"117-124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas"],"prefix":"10.1111","volume":"95","author":[{"given":"Janaina","family":"Petenuci","sequence":"first","affiliation":[{"name":"Unidade de Suprarrenal Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42 Servi\u00e7o de Endocrinologia e Metabologia Hospital das Cl\u00ednicas Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto 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