Medulloblastoma Associated with Down Syndrome: From a Rare Event Leading to a Pathogenic Hypothesis
Alessandra Boni,
Marco Ranalli,
Giada Del Baldo,
Roberto Carta,
Mariachiara Lodi,
Emanuele Agolini,
Martina Rinelli,
Diletta Valentini,
Sabrina Rossi,
Viola Alesi,
Antonella Cacchione,
Evelina Miele,
Iside Alessi,
Anna Maria Caroleo,
Giovanna Stefania Colafati,
Maria Antonietta De Ioris,
Luigi Boccuto,
Mario Balducci,
Andrea Carai,
Angela Mastronuzzi
Affiliations
Alessandra Boni
Department of Pediatrics, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy
Marco Ranalli
Department of Pediatrics, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy
Giada Del Baldo
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Roberto Carta
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Mariachiara Lodi
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Emanuele Agolini
Laboratory of Medical Genetics, IRCCS Bambino Gesù Children’s Hospital, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Martina Rinelli
Laboratory of Medical Genetics, IRCCS Bambino Gesù Children’s Hospital, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Diletta Valentini
Pediatric and Infectious Disease Unit, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Sabrina Rossi
Department of Laboratories, Pathology Unit, Bambino Gesù Children’s Hospital, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Viola Alesi
Laboratory of Medical Genetics, IRCCS Bambino Gesù Children’s Hospital, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Antonella Cacchione
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Evelina Miele
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Iside Alessi
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Anna Maria Caroleo
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Giovanna Stefania Colafati
Neuroradiology Unit, Department of Imaging, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Maria Antonietta De Ioris
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Luigi Boccuto
School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC 29634, USA
Mario Balducci
Department of Imaging, Radiation Oncology and Haematology, Policlinico A. Gemelli Fundation, IRCCS, Catholic University of Sacred Heart, Largo A. Gemelli 1, 00168 Rome, Italy
Andrea Carai
Neurosurgery Unit, Department of Neurological and Psychiatric Sciences, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
Angela Mastronuzzi
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital IRCCS, Piazza Sant’Onofrio 4, 00146 Rome, Italy
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.
