Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history. Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis. Universal screening could be an option to address the problem of underdiagnosis.

中文翻译：

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缺乏阿姆斯特丹 II 或贝塞斯达标准的林奇综合征患者的诊断

林奇综合征 (LS) 是一种常染色体显性遗传性疾病，其特征是具有患癌症的遗传倾向，由错配修复系统基因的致病性变异引起。通过实施阿姆斯特丹 II 和修订后的贝塞斯达标准来发现病例，这些标准基于家族史。符合标准的患者接受后验，例如种系 DNA 测序，以确认诊断。然而，这些标准的敏感性较差，因为超过四分之一的 LS 患者不符合标准。该标准缺乏敏感性很可能是由于该综合征的不完全外显率。特定类型癌症的外显率和风险高度依赖于受影响的基因以及可能的变异。具有低外显率基因变异的患者患 LS 相关癌症的风险较低，导致家庭中的几代人未受影响，并且显示出较少的明确模式。本研究的重点是描述 LS 病例的遗传因素，这些因素导致其诊断所用的临床标准缺乏敏感性。普遍筛查可能是解决诊断不足问题的一种选择。