{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:40:39Z","timestamp":1792129239678,"version":"4.4.0"},"reference-count":13,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n To improve diagnostics of cancer predisposition syndromes (CPSs) in children with cancer, it is essential to evaluate the effect of CPS gene sequencing among all children with cancer and compare it with genetic testing based on clinical selection. However, a reliable comparison is difficult because recent reports on a phenotype-first approach in large, unselected childhood cancer cohorts are lacking.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To describe a national children\u2019s cancer center\u2019s experience in diagnosing CPSs before introducing routine next-generation sequencing.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study was conducted at the National Retinoblastoma Treatment Center (Amsterdam, the Netherlands) and the Princess M\u00e1xima Center for Pediatric Oncology (Utrecht, Netherlands) and included Dutch pediatric patients with a new diagnosis of neoplasm between June 1, 2018, and December 31, 2019. Follow-up was at least 18 months after neoplasm diagnosis. Data analysis was conducted from July 2021 to February 2022.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n As part of routine diagnostics, pediatric oncologists and ophthalmologists checked for characteristics of CPSs and selected children for referral to clinical geneticists and genetic testing.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Detected cancer predisposition syndromes.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 824 patients (median [range] age at diagnosis 7.5 [0-18.9] years; 361 girls [44%]) were assessed, including 335 children with a hematological neoplasm (41%) and 489 (59%) with a solid tumor. In 71 of 824 children (8.6%), a CPS was identified, of which most (96%) were identified by a phenotype-driven approach. Down syndrome and neurofibromatosis type 1 were the most common CPSs diagnosed. In 42 of 71 patients (59%), a CPS was identified after these children developed a neoplasm. The specific type of neoplasm was the most frequent indicator for genetic testing, whereas family history played a minor role.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study of children with a neoplasm, the prevalence of CPSs identified by a phenotype-driven approach was 8.6%. The diagnostic approach for identifying CPSs is currently shifting toward a genotype-first approach. Future studies are needed to determine the diagnostic value, as well as possible disadvantages of CPS gene sequencing among all children with cancer compared with the phenotype-driven approach.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.54157","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T11:02:02Z","timestamp":1675422122000},"page":"e2254157","source":"Crossref","is-referenced-by-count":51,"title":["Assessment of Cancer Predisposition Syndromes in a National Cohort of Children With a Neoplasm"],"prefix":"10.1001","volume":"6","author":[{"given":"Jette J.","family":"Bakhuizen","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M. J.","family":"Hopman","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machteld I.","family":"Bosscha","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J.","family":"Dommering","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marry M.","family":"van den Heuvel-Eibrink","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"University Medical Center-Wilhelmina Children\u2019s Hospital, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna A.","family":"Hol","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart A.","family":"Kester","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco J.","family":"Koudijs","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin P. S.","family":"Langenberg","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan L. C.","family":"Loeffen","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"van der Lugt","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette C.","family":"Moll","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max M.","family":"van Noesel","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"},{"name":"Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie E.","family":"Smetsers","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"de Vos-Kerkhof","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes H. 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