{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:30:53Z","timestamp":1784032253344,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition syndrome pattern: a higher risk to develop acute leukemia and a lower incidence of solid tumors. In particular, brain tumors are rarely reported in the DS population, and biological behavior and natural history are not well described and identified. We report a case of a 10-year-old child with DS who presented with a medulloblastoma (MB). Histological examination revealed a classic MB with focal anaplasia and the molecular profile showed the presence of a CTNNB1 variant associated with the wingless (WNT) molecular subgroup with a good prognosis in contrast to our case report that has shown an early metastatic relapse. The nearly seven-fold decreased risk of MB in children with DS suggests the presence of protective biological mechanisms. The cerebellum hypoplasia and the reduced volume of cerebellar granule neuron progenitor cells seem to be a possible favorable condition to prevent MB development via inhibition of neuroectodermal differentiation. Moreover, the NOTCH\/WNT dysregulation in DS, which is probably associated with an increased risk of leukemia, suggests a pivotal role of this pathway alteration in the pathogenesis of MB; therefore, this condition should be further investigated in future studies by molecular characterizations.<\/jats:p>","DOI":"10.3390\/diagnostics11020254","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T20:51:51Z","timestamp":1612817511000},"page":"254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Medulloblastoma Associated with Down Syndrome: From a Rare Event Leading to a Pathogenic Hypothesis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8723-7224","authenticated-orcid":false,"given":"Alessandra","family":"Boni","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ranalli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3540-4331","authenticated-orcid":false,"given":"Giada","family":"Del Baldo","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Lodi","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-6225","authenticated-orcid":false,"given":"Emanuele","family":"Agolini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, IRCCS Bambino Ges\u00f9 Children\u2019s Hospital, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rinelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, IRCCS Bambino Ges\u00f9 Children\u2019s Hospital, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Valentini","sequence":"additional","affiliation":[{"name":"Pediatric and Infectious Disease Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Laboratories, Pathology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7514-5683","authenticated-orcid":false,"given":"Viola","family":"Alesi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, IRCCS Bambino Ges\u00f9 Children\u2019s Hospital, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Cacchione","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-1032","authenticated-orcid":false,"given":"Evelina","family":"Miele","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iside","family":"Alessi","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-7301","authenticated-orcid":false,"given":"Anna Maria","family":"Caroleo","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-4904","authenticated-orcid":false,"given":"Giovanna Stefania","family":"Colafati","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Department of Imaging, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2113-4505","authenticated-orcid":false,"given":"Maria Antonietta","family":"De Ioris","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Boccuto","sequence":"additional","affiliation":[{"name":"School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC 29634, USA"},{"name":"JC Self Research Institute of the Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Balducci","sequence":"additional","affiliation":[{"name":"Department of Imaging, Radiation Oncology and Haematology, Policlinico A. Gemelli Fundation, IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5203-7855","authenticated-orcid":false,"given":"Andrea","family":"Carai","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Department of Neurological and Psychiatric Sciences, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4408-2373","authenticated-orcid":false,"given":"Angela","family":"Mastronuzzi","sequence":"additional","affiliation":[{"name":"Department of Onco-Hematology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Piazza Sant\u2019Onofrio 4, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12929-015-0138-y","article-title":"Down syndrome: An insight of the disease","volume":"22","author":"Asim","year":"2015","journal-title":"J. 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