Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, University Children's Hospital, Heinrich-Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Department of Diagnostic and Interventional Radiology, Medical Faculty, University of Duesseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.
Fam Cancer. 2019 Jul;18(3):353-358. doi: 10.1007/s10689-019-00121-z.
Medulloblastoma is the most frequent malignant brain tumor in childhood. This highly malignant neoplasm occurs usually before 10 years of age and more frequently in boys. The 5-year event-free survival rate for high-risk medulloblastoma is low at 62% despite a multimodal therapy including surgical resection, radiation therapy and chemotherapy. We report the case of a boy, who was born to consanguineous parents. Prominently, he had multiple café-au-lait spots. At the age of 3 years he was diagnosed with a high-risk metastatic medulloblastoma. The patient died only 11 months after diagnosis of a fulminant relapse presenting as meningeal and spinal dissemination. Whole-exome sequencing of germline DNA was employed to detect the underlying mutation for this putative cancer syndrome presenting with the combination of medulloblastoma and skin alterations. After screening all possible homozygous gene SNVs, we identified a mutation of SON, an essential protein in cell cycle regulation and cell proliferation, as the most likely genetic cause.
髓母细胞瘤是儿童中最常见的恶性脑肿瘤。这种高度恶性的肿瘤通常发生在 10 岁之前，男孩中更常见。尽管采用了包括手术切除、放疗和化疗在内的多模式治疗，但高危髓母细胞瘤的 5 年无事件生存率仍较低，仅为 62%。我们报告了一例男孩的病例，他出生于近亲父母。值得注意的是，他有多处咖啡牛奶斑。3 岁时，他被诊断为高危转移性髓母细胞瘤。在诊断后仅 11 个月，患者因脑膜和脊髓播散的暴发性复发而死亡。对生殖系 DNA 进行全外显子组测序，以检测可能存在的癌症综合征的潜在突变，该综合征表现为髓母细胞瘤和皮肤改变的组合。在筛选所有可能的纯合基因突变 SNVs 后，我们确定了 SON 的突变，SON 是细胞周期调节和细胞增殖中的必需蛋白，是最可能的遗传原因。
