{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:48:49Z","timestamp":1781563729417,"version":"3.54.5"},"reference-count":39,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["T2\/93\/Gr1; 50-2709-Gr2"],"award-info":[{"award-number":["T2\/93\/Gr1; 50-2709-Gr2"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>(1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP\/GPOH studies. (3) Results: Genitourinary malformations (GU, N = 66, 2.3%), Beckwith-Wiedemann spectrum (BWS, N = 32, 1.1%), isolated hemihypertrophy (IHH, N = 29, 1.0%), Denys-Drash syndrome (DDS, N = 24, 0.8%) and WAGR syndrome (N = 20, 0.7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2% vs. 18%), but more often nephroblastomatosis (12.9% vs. 1.9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4% increase) and favorable in BWS (86.9% reduction). The event-free survival (EFS) of patients with BWS was significantly (p = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.<\/jats:p>","DOI":"10.3390\/cancers13195016","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"5016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Characteristics of Nephroblastoma\/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Nils","family":"Welter","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-8343","authenticated-orcid":false,"given":"Rhoikos","family":"Furtw\u00e4ngler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Melchior","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Kager","sequence":"additional","affiliation":[{"name":"St. Anna Kinderspital, Department of Pediatrics, Medical University Vienna, Kinderspitalgasse 6, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vokuhl","sequence":"additional","affiliation":[{"name":"Section of Pediatric Pathology, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0588-0225","authenticated-orcid":false,"given":"Jens-Peter","family":"Schenk","sequence":"additional","affiliation":[{"name":"Division of Pediatric Radiology, Clinic for Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-6302","authenticated-orcid":false,"given":"Clemens Magnus","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Vascular and Pediatric Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Siemer","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7915-6045","authenticated-orcid":false,"given":"Manfred","family":"Gessler","sequence":"additional","affiliation":[{"name":"Developmental Biochemistry and Comprehensive Cancer Center Mainfranken, Theodor-Boveri-Institute\/Biocenter, University of W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-323X","authenticated-orcid":false,"given":"Norbert","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1365-3016.1994.tb00439.x","article-title":"International variations in the incidence of childhood soft-tissue sarcomas","volume":"8","author":"Stiller","year":"1994","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1093\/annonc\/mds025","article-title":"Treatment and outcome of Wilms\u2019 tumour patients: An analysis of all cases registered in the UKW3 trial","volume":"23","author":"Moroz","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1200\/JCO.2015.62.1888","article-title":"Advances in wilms tumor treatment and biology: Progress through international collaboration","volume":"33","author":"Dome","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nrurol.2017.163","article-title":"Position Paper: Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol","volume":"14","author":"Hol","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_5","first-page":"474","article-title":"Congenital anomalies and childhood cancer in Great Britain","volume":"60","author":"Narod","year":"1997","journal-title":"Am.J.Hum.Genet."},{"key":"ref_6","first-page":"132","article-title":"High Incidence of Malformation Syndromes in a Series of 1, 073 Child","volume":"143","author":"Merks","year":"2005","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/adc.57.9.685","article-title":"Wilms\u2019s tumour and aniridia: Clinical and cytogenetic features","volume":"57","author":"Shannon","year":"1982","journal-title":"Arch. Dis. Child."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/cncr.33304","article-title":"Clinical characteristics and outcomes of children with WAGR syndrome and Wilms tumor and\/or nephroblastomatosis: The 30-year SIOP-RTSG experience","volume":"127","author":"Hol","year":"2021","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1200\/JCO.2003.06.096","article-title":"Characteristics and outcomes of children with the Wilms tumor-aniridia syndrome: A report from the National Wilms Tumor Study Group","volume":"21","author":"Breslow","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0022-3476(70)80409-7","article-title":"A syndrome of pseudohermaphroditism, Wilms\u2019 tumor, hypertension, and degenerative renal disease","volume":"76","author":"Drash","year":"1970","journal-title":"J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1136\/jmg.31.6.471","article-title":"the month The Denys-Drash syndrome","volume":"36","author":"Mueller","year":"1994","journal-title":"J. Med Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1136\/jmg.2006.041723","article-title":"Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour","volume":"43","author":"Scott","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/346194a0","article-title":"The candidate Wilms\u2019 tumour gene is involved in genitourinary development","volume":"346","author":"Fleming","year":"1990","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/gcc.2870030203","article-title":"Direct pulsed field gel electrophoresis of Wilms\u2019 tumors shows that dna deletions in 11 p 13 are rare","volume":"3","author":"Ragg","year":"1991","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/(SICI)1096-8628(19981002)79:4<274::AID-AJMG8>3.0.CO;2-M","article-title":"Isolated hemihyperplasia (hemihypertrophy): Report of a prospective multicenter study of the incidence of neoplasia and review","volume":"79","author":"Hoyme","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1086\/497540","article-title":"Children with Idiopathic Hemihypertrophy and Beckwith-Wiedemann Syndrome Have Different Constitutional Epigenotypes Associated with Wilms Tumor","volume":"77","author":"Grundy","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/BF00282078","article-title":"Wiedemann-Beckwith syndrome: Presentation of clinical and cytogenetic data on 22 new cases and review of the literature","volume":"74","author":"Pettenati","year":"1986","journal-title":"Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41574-019-0180-z","article-title":"Overgrowth syndromes\u2014Clinical and molecular aspects and tumour risk","volume":"15","author":"Brioude","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.14694\/EdBook_AM.2014.34.215","article-title":"Risk Stratification for Wilms Tumor: Current Approach and Future Directions","volume":"34","author":"Dome","year":"2014","journal-title":"Am. Soc. Clin. Oncol. Educ. B."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1007\/s00432-019-03038-3","article-title":"The effectiveness of Wilms tumor screening in Beckwith\u2013Wiedemann spectrum","volume":"145","author":"Mussa","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/(SICI)1096-8628(19981002)79:4<268::AID-AJMG7>3.0.CO;2-I","article-title":"Nephrogenic rests and the pathogenesis of Wilms tumor: Developmental and clinical considerations","volume":"79","author":"Beckwith","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/mpo.2950200404","article-title":"Genetics and epidemiology of Wilms\u2019 tumor: The French Wilms\u2019 tumor study","volume":"20","author":"Chompret","year":"1992","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3634","DOI":"10.1200\/JCO.1998.16.11.3634","article-title":"Constitutional WT1 mutations in Wilms\u2019 tumor patients","volume":"16","author":"Diller","year":"1998","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/pbc.21759","article-title":"Management of Wilms tumors in Drash and Frasier syndromes","volume":"52","author":"Auber","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.1200\/JCO.2004.02.136","article-title":"Frequency and Heritability of WT1 Mutations in Nonsyndromic Wilms\u2019 Tumor Patients: A UK Children\u2019s Cancer Study Group Study","volume":"22","author":"Little","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/0092-8674(91)90194-4","article-title":"Germline mutations in the Wilms\u2019 tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome","volume":"67","author":"Pelletier","year":"1991","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/cncr.23672","article-title":"Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein \u03b21 gene CTNNB1 for patients with Wilms tumors","volume":"113","author":"Weirich","year":"2008","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0022-3476(80)80322-2","article-title":"Complete and incomplete forms of Beckwith-Wiedemann syndrome: Their oncogenic potential","volume":"96","author":"Fowler","year":"1980","journal-title":"J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S0022-3476(98)70008-3","article-title":"Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry","volume":"132","author":"DeBaun","year":"1998","journal-title":"J. Pediatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/mpo.2950210307","article-title":"Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with wilms tumor: A report from the national Wilms tumor study","volume":"21","author":"Green","year":"1993","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/15513819009067094","article-title":"Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms\u2019 tumor","volume":"10","author":"Beckwith","year":"1990","journal-title":"Pediatr. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"MacFarland, S.P., Duffy, K.A., Bhatti, T.R., Bagatell, R., Balamuth, N.J., Brodeur, G.M., Ganguly, A., Mattei, P.A., Surrey, L.F., and Balis, F.M. (2018). Diagnosis of Beckwith-Wiedemann syndrome in children presenting with Wilms tumor. Pediatr. Blood Cancer, e27296.","DOI":"10.1002\/pbc.27296"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrendo.2017.166","article-title":"Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith\u2013Wiedemann syndrome: An international consensus statement","volume":"14","author":"Brioude","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/ajmg.a.38142","article-title":"Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology","volume":"173","author":"Ripperger","year":"2017","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/cncr.23672","article-title":"Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein beta1 gene CTNNB1 for patients with Wilms tumors: Results of long-term surveillance of 71 patients from International Society of Pediatric Oncolog","volume":"113","author":"Weirich","year":"2008","journal-title":"Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/pbc.22496","article-title":"Stromal and epithelial predominant Wilms tumours have an excellent outcome: The SIOP 93 01 experience","volume":"55","author":"Verschuur","year":"2010","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1055\/s-0034-1371840","article-title":"Pretreatment for bilateral nephroblastomatosis is an independent risk factor for progressive disease in patients with stage V nephroblastoma","volume":"226","author":"Schmolze","year":"2014","journal-title":"Klin. Padiatr."},{"key":"ref_38","first-page":"885","article-title":"Sydromes and syndrome-like features in bilateral Wilms Tumor are associated with inferior outcome","volume":"55","author":"Nourkami","year":"2010","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_39","first-page":"S34","article-title":"Treatment of Nephroblastomatosis: The GPOH Experience 1993\u20132014","volume":"63","author":"Warmann","year":"2016","journal-title":"Pediatr. Blood Cancer"}],"updated-by":[{"DOI":"10.3390\/cancers13225743","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000}}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/19\/5016\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T22:27:13Z","timestamp":1754260033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/19\/5016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":39,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["cancers13195016"],"URL":"https:\/\/doi.org\/10.3390\/cancers13195016","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202108.0223.v1","asserted-by":"object"}]},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,7]]}}}