Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group
Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group
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DOI：
10.1136/jmedgenet-2020-107627
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发表时间：
2021-02-23
影响因子：
4
通讯作者：
Tabori, Uri
中科院分区：
文献类型：
--
作者：
Aronson, Melyssa;Colas, Chrystelle;Tabori, Uri
背景体质性错配修复缺陷综合征（CMMRD）是与多器官肿瘤相关的最具侵袭性的癌症易感综合征，常在儿童期出现。在年龄和癌症的表现以及类似1型神经纤维瘤病的良性表现方面存在差异。基因检测可能不提供信息，并且与最常见的相关基因PMS2相关的假基因使其复杂化。迄今为止，尚无诊断标准。由于监测和基于免疫的治疗是可用的，建立CMMRD诊断是提高生存率的关键。方法为了建立一个稳健的诊断路径，组成了一个多学科的国际工作组，由两个最大的联盟（国际复制修复缺陷联盟（IRRD）和欧洲CMMRD护理联盟（C4CMMRD））的代表组成，以建立基于专业知识、文献回顾和共识的诊断标准。结果工作组建立了CMMRD的7个诊断标准，包括4个确定性标准（强证据）和3个可能性标准（中等证据）。所有标准均保证CMMRD监督。该标准包括生殖细胞错配修复结果，辅助检查和临床表现，以确定诊断。CMMRD的标志性癌症由工作组在广泛的文献综述和与IRRD和C4CMMRD联盟的协商后定义。结论本立场文件总结了证据和理由，为CMMRD诊断提供了具体的指导方针，这需要适当的监测和治疗。
Background Constitutional mismatch repair deficiency syndrome (CMMRD) is the most aggressive cancer predisposition syndrome associated with multiorgan cancers, often presenting in childhood. There is variability in age and presentation of cancers and benign manifestations mimicking neurofibromatosis type 1. Genetic testing may not be informative and is complicated by pseudogenes associated with the most commonly associated gene, PMS2. To date, no diagnostic criteria exist. Since surveillance and immune-based therapies are available, establishing a CMMRD diagnosis is key to improve survival. Methods In order to establish a robust diagnostic path, a multidisciplinary international working group, with representation from the two largest consortia (International Replication Repair Deficiency (IRRD) consortium and European Consortium Care for CMMRD (C4CMMRD)), was formed to establish diagnostic criteria based on expertise, literature review and consensus. Results The working group established seven diagnostic criteria for the diagnosis of CMMRD, including four definitive criteria (strong evidence) and three likely diagnostic criteria (moderate evidence). All criteria warrant CMMRD surveillance. The criteria incorporate germline mismatch repair results, ancillary tests and clinical manifestation to determine a diagnosis. Hallmark cancers for CMMRD were defined by the working group after extensive literature review and consultation with the IRRD and C4CMMRD consortia. Conclusions This position paper summarises the evidence and rationale to provide specific guidelines for CMMRD diagnosis, which necessitates appropriate surveillance and treatment.