Boni Alessandra, Ranalli Marco, Del Baldo Giada, Carta Roberto, Lodi Mariachiara, Agolini Emanuele, Rinelli Martina, Valentini Diletta, Rossi Sabrina, Alesi Viola, Cacchione Antonella, Miele Evelina, Alessi Iside, Caroleo Anna Maria, Colafati Giovanna Stefania, De Ioris Maria Antonietta, Boccuto Luigi, Balducci Mario, Carai Andrea, Mastronuzzi Angela
Department of Pediatrics, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital IRCCS, Piazza Sant'Onofrio 4, 00146 Rome, Italy.
Diagnostics (Basel). 2021 Feb 7;11(2):254. doi: 10.3390/diagnostics11020254.
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 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.
唐氏综合征（DS）是最常见的染色体异常疾病，具有独特的癌症易感性综合征模式：患急性白血病的风险较高，实体瘤的发病率较低。特别是，唐氏综合征人群中脑肿瘤的报道很少，其生物学行为和自然史也没有得到很好的描述和确定。我们报告了一例10岁唐氏综合征儿童患髓母细胞瘤（MB）的病例。组织学检查显示为典型的髓母细胞瘤伴局灶性间变，分子谱显示存在与无翅（WNT）分子亚组相关的变异，预后良好，而我们的病例报告显示早期发生转移复发。唐氏综合征儿童患髓母细胞瘤的风险降低近7倍，提示存在保护性生物学机制。小脑发育不全以及小脑颗粒神经元祖细胞体积减小似乎是通过抑制神经外胚层分化来预防髓母细胞瘤发生的一种可能的有利条件。此外，唐氏综合征中NOTCH/WNT信号失调可能与白血病风险增加有关，提示该信号通路改变在髓母细胞瘤发病机制中起关键作用；因此，未来研究应通过分子特征进一步对此情况进行研究。
