{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T20:59:20Z","timestamp":1784581160018,"version":"3.55.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006244","name":"Stichting Kinderen Kankervrij","doi-asserted-by":"publisher","award":["143"],"award-info":[{"award-number":["143"]}],"id":[{"id":"10.13039\/501100006244","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Familial Cancer"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208\/363) were assessed positive. In 15% of patients (32\/208), the 2D photographic series with (n\u2009=\u200912) or without (n\u2009=\u200920) 3D photographs were decisive in the positive assessment. In 2% (4\/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4\/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort.<\/jats:p>","DOI":"10.1007\/s10689-021-00237-1","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T02:02:26Z","timestamp":1615255346000},"page":"263-271","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical value of a screening tool for tumor predisposition syndromes in childhood cancer patients (TuPS): a prospective, observational, multi-center study"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-0560","authenticated-orcid":false,"given":"Floor A. M.","family":"Postema","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M. J.","family":"Hopman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corianne A. J. M.","family":"de Borgie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora M.","family":"Aalfs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob K.","family":"Anninga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieke P. V.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fonnet E.","family":"Bleeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J.","family":"Dommering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha K. A.","family":"van Eijkelenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marry M.","family":"van den Heuvel-Eibrink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna A.","family":"Hol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wijnanda A.","family":"Kors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom G. W.","family":"Letteboer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan L. C. M.","family":"Loeffen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisethe","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maran J. W.","family":"Olderode-Berends","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul C.","family":"Hennekam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes H. M.","family":"Merks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"issue":"2","key":"237_CR1","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/ajmg.a.30603","volume":"134A","author":"JH Merks","year":"2005","unstructured":"Merks JH, Caron HN, Hennekam RC (2005) High incidence of malformation syndromes in a series of 1,073 children with cancer. Am J Med Genet A 134A(2):132\u2013143","journal-title":"Am J Med Genet A"},{"issue":"24","key":"237_CR2","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1056\/NEJMoa1508054","volume":"373","author":"J Zhang","year":"2015","unstructured":"Zhang J, Walsh MF, Wu G et al (2015) Germline mutations in predisposition genes in pediatric cancer. N Engl J Med 373(24):2336\u20132346","journal-title":"N Engl J Med"},{"key":"237_CR3","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5699","author":"DW Parsons","year":"2016","unstructured":"Parsons DW, Roy A, Yang Y et al (2016) Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol. https:\/\/doi.org\/10.1001\/jamaoncol.2015.5699","journal-title":"JAMA Oncol"},{"issue":"7696","key":"237_CR4","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature25480","volume":"555","author":"SN Grobner","year":"2018","unstructured":"Grobner SN, Worst BC, Weischenfeldt J et al (2018) The landscape of genomic alterations across childhood cancers. Nature 555(7696):321\u2013327","journal-title":"Nature"},{"key":"237_CR5","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41525-018-0070-7","volume":"3","author":"SH Chan","year":"2018","unstructured":"Chan SH, Chew W, Ishak NDB et al (2018) Clinical relevance of screening checklists for detecting cancer predisposition syndromes in Asian childhood tumours. NPJ Genomic Med 3:30","journal-title":"NPJ Genomic Med"},{"issue":"3","key":"237_CR6","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.ejmg.2016.01.008","volume":"59","author":"MC Jongmans","year":"2016","unstructured":"Jongmans MC, Loeffen JL, Waanders E et al (2016) Recognition of genetic predisposition in pediatric cancer patients: an easy-to-use selection tool. Eur J Med Genet 59(3):116\u2013125","journal-title":"Eur J Med Genet"},{"key":"237_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26718","author":"FAM Postema","year":"2017","unstructured":"Postema FAM, Hopman SMJ, Hennekam RC, Merks JHM (2017) Consequences of diagnosing a tumor predisposition syndrome in children with cancer: a literature review. Pediatr Blood Cancer. https:\/\/doi.org\/10.1002\/pbc.26718","journal-title":"Pediatr Blood Cancer"},{"issue":"1","key":"237_CR8","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/gim.2014.147","volume":"17","author":"H Hampel","year":"2015","unstructured":"Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL (2015) A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med 17(1):70\u201387","journal-title":"Genet Med"},{"issue":"4","key":"237_CR9","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1002\/ajmg.a.38142","volume":"173","author":"T Ripperger","year":"2017","unstructured":"Ripperger T, Bielack SS, Borkhardt A et al (2017) Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology. Am J Med Genet A 173(4):1017\u20131037","journal-title":"Am J Med Genet A"},{"issue":"4","key":"237_CR10","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/S1470-2045(05)70076-0","volume":"6","author":"C Orellana","year":"2005","unstructured":"Orellana C (2005) Malformation syndromes during cancer in childhood. Lancet Oncol 6(4):198","journal-title":"Lancet Oncol"},{"issue":"10","key":"237_CR11","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1002\/ajmg.a.31674","volume":"143","author":"RC Hennekam","year":"2007","unstructured":"Hennekam RC (2007) What to call a syndrome. Am J Med Genet A. 143(10):1021\u20131024","journal-title":"Am J Med Genet A."},{"key":"237_CR12","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.ejca.2017.04.021","volume":"80","author":"FAM Postema","year":"2017","unstructured":"Postema FAM, Hopman SMJ, Aalfs CM et al (2017) Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation. Eur J Cancer 80:48\u201354","journal-title":"Eur J Cancer"},{"issue":"15","key":"237_CR13","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.1016\/j.ejca.2013.06.015","volume":"49","author":"SM Hopman","year":"2013","unstructured":"Hopman SM, Merks JH, de Borgie CA et al (2013) The development of a clinical screening instrument for tumour predisposition syndromes in childhood cancer patients. Eur J Cancer 49(15):3247\u20133254","journal-title":"Eur J Cancer"},{"issue":"2","key":"237_CR14","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1002\/(SICI)1096-8628(19990625)89:2<81::AID-AJMG5>3.0.CO;2-I","volume":"89","author":"CL Clericuzio","year":"1999","unstructured":"Clericuzio CL (1999) Recognition and management of childhood cancer syndromes: a systems approach. Am J Med Genet 89(2):81\u201390","journal-title":"Am J Med Genet"},{"issue":"1","key":"237_CR15","doi-asserted-by":"publisher","first-page":"e013237","DOI":"10.1136\/bmjopen-2016-013237","volume":"7","author":"FA Postema","year":"2017","unstructured":"Postema FA, Hopman SM, de Borgie CA et al (2017) Validation of a clinical screening instrument for tumour predisposition syndromes in patients with childhood cancer (TuPS): protocol for a prospective, observational, multicentre study. BMJ Open 7(1):e013237","journal-title":"BMJ Open"},{"key":"237_CR16","unstructured":"IKN Oncoline Richtlijnen Oncologische zorg. https:\/\/www.oncoline.nl\/. Accessed 1 Nov 2020"},{"key":"237_CR17","unstructured":"Stichting Opsporing Erfelijke Tumoren en Vereniging Klinische Genetica Nederland, Werkgroep Klinische Oncogenetica (2017) Erfelijke en familiare tumoren, richtlijnen voor diagnostiek en preventie. https:\/\/www.stoet.nl\/wp-content\/uploads\/2017\/04\/STOET-Richtlijnenboekje-april2017_DEF.pdf"},{"issue":"6","key":"237_CR18","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1136\/jmedgenet-2014-102264","volume":"51","author":"CJ Dommering","year":"2014","unstructured":"Dommering CJ, Mol BM, Moll AC et al (2014) RB1 mutation spectrum in a comprehensive nationwide cohort of retinoblastoma patients. J Med Genet 51(6):366\u2013374","journal-title":"J Med Genet"},{"key":"237_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26441","author":"C Goudie","year":"2017","unstructured":"Goudie C, Coltin H, Witkowski L, Mourad S, Malkin D, Foulkes WD (2017) The McGill Interactive Pediatric OncoGenetic Guidelines: an approach to identifying pediatric oncology patients most likely to benefit from a genetic evaluation. Pediatr Blood Cancer. https:\/\/doi.org\/10.1002\/pbc.26441","journal-title":"Pediatr Blood Cancer"},{"issue":"1","key":"237_CR20","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/pbc.23283","volume":"58","author":"S Knapke","year":"2012","unstructured":"Knapke S, Nagarajan R, Correll J, Kent D, Burns K (2012) Hereditary cancer risk assessment in a pediatric oncology follow-up clinic. Pediatr Blood Cancer 58(1):85\u201389","journal-title":"Pediatr Blood Cancer"},{"key":"237_CR21","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.canep.2018.05.006","volume":"55","author":"W Jastaniah","year":"2018","unstructured":"Jastaniah W, Aljefri A, Ayas M et al (2018) Prevalence of hereditary cancer susceptibility syndromes in children with cancer in a highly consanguineous population. Cancer Epidemiol 55:88\u201395","journal-title":"Cancer Epidemiol"},{"issue":"2","key":"237_CR22","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S2352-4642(20)30275-3","volume":"5","author":"CP Kratz","year":"2021","unstructured":"Kratz CP, Jongmans MC, Cav\u00e9 H et al (2021) Predisposition to cancer in children and adolescents. Lancet Child Adolesc Health 5(2):142\u2013154","journal-title":"Lancet Child Adolesc Health"}],"container-title":["Familial Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10689-021-00237-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10689-021-00237-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10689-021-00237-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T07:43:04Z","timestamp":1632987784000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10689-021-00237-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,9]]},"references-count":22,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["237"],"URL":"https:\/\/doi.org\/10.1007\/s10689-021-00237-1","relation":{},"ISSN":["1389-9600","1573-7292"],"issn-type":[{"value":"1389-9600","type":"print"},{"value":"1573-7292","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,9]]},"assertion":[{"value":"26 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by The Medical Ethical Committee of the Amsterdam University Medical Center.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent is obtained from all patients and parents when 12\u00a0years or older, or by parents alone when the patient was younger than 12\u00a0years, according to Dutch law.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}