Daou Badih, Zanello Marc, Varlet Pascale, Brugieres Laurence, Jabbour Pascal, Caron Olivier, Lavoine Noémie, Dhermain Frederic, Willekens Christophe, Beuvon Frederic, Malka David, Lechapt-Zalcmann Emmanuèle, Abi Lahoud Georges
*Department of Neurosurgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania; ‡Department of Neurosurgery, Sainte-Anne University Hospital, Paris, France; §Paris Descartes University, Paris, France; ¶Department of Neuropathology, Sainte-Anne Hospital, Paris, France; ‖Department of Pediatric Oncology, Gustave Roussy Institute, Villejuif, France; #Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France; **Department of Radiotherapy, Gustave Roussy Institute, Villejuif, France; ‡‡Department of Hematology, Gustave Roussy Institute, Villejuif, France; §§Department of Pathology, Cochin Hospital, Paris, France; ¶¶Department of Gastroenterology, Gustave Roussy Institute, Villejuif, France; ‖‖Department of Pathology, Caen University Hospital, Caen, France.
Neurosurgery. 2015 Jul;77(1):E145-52; discussion E152. doi: 10.1227/NEU.0000000000000754.
Constitutional mismatch repair deficiency (CMMRD) syndrome is a disorder with recessive inheritance caused by biallelic mismatch repair gene mutations, in which mismatch repair defects are inherited from both parents. This syndrome is associated with multiple cancers occurring in childhood. The most common tumors observed with CMMRD include brain tumors, digestive tract tumors, and hematological malignancies. The aim of this study was to report new phenotypic expressions of CMMRD syndrome and add new insight to the existing knowledge about this disease. A review of the literature was conducted and recommendation for surveillance and follow-up in patients with CMMRD are proposed.
We report for the first time in the literature, the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome, with the development of 2 unusual tumors: an anaplastic ganglioglioma and an osteosarcoma. She presented initially with an anaplastic ganglioglioma and later developed several malignancies including colonic adenocarcinoma, osteosarcoma, and acute myeloid leukemia. The patient had an atypical course of her disease with development of the initial malignancy at an older age and a remarkably long survival period despite developing aggressive tumors.
Many aspects of this disease are still unknown. We identified a case of CMMRD in a patient presenting with an anaplastic ganglioglioma, who underwent successful surgical resection, chemotherapy, and radiotherapy and has had one of the longest survival periods known with this disease. This case broadens the tumor spectrum observed with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new phenotypic expressions of this genetic defect.
先天性错配修复缺陷（CMMRD）综合征是一种由双等位基因错配修复基因突变引起的隐性遗传性疾病，其中错配修复缺陷从父母双方遗传而来。该综合征与儿童期发生的多种癌症相关。CMMRD最常见的肿瘤包括脑肿瘤、消化道肿瘤和血液系统恶性肿瘤。本研究的目的是报告CMMRD综合征的新表型表达，并为关于该疾病的现有知识增添新见解。进行了文献综述，并提出了对CMMRD患者进行监测和随访的建议。
我们在文献中首次报告了一例22岁女性患者，她被诊断为CMMRD综合征，并出现了2种不寻常的肿瘤：间变性节细胞胶质瘤和骨肉瘤。她最初表现为间变性节细胞胶质瘤，后来发展为多种恶性肿瘤，包括结肠腺癌、骨肉瘤和急性髓系白血病。该患者疾病病程不典型，初始恶性肿瘤在较年长时发生，尽管出现侵袭性肿瘤但生存期显著延长。
该疾病的许多方面仍然未知。我们在一名表现为间变性节细胞胶质瘤的患者中发现了一例CMMRD，该患者接受了成功的手术切除、化疗和放疗，并且是已知患有该疾病生存期最长的患者之一。该病例拓宽了CMMRD综合征所观察到的肿瘤谱，间变性节细胞胶质瘤和骨肉瘤作为这种基因缺陷的新表型表达。
