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Abstract：
Recognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208/363) were assessed positive. In 15% of patients (32/208), the 2D photographic series with (n = 12) or without (n = 20) 3D photographs were decisive in the positive assessment. In 2% (4/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort.
摘要：
识别患有癌症的儿童的肿瘤易感性综合征（TPS）具有临床意义。早些时候，我们开发了一种筛查工具，以提高诊断准确性和临床效率，以识别患有癌症的儿童的TPS。在这里，我们报告了该工具在临床实践中的价值。TuPS是一个潜在的，观察,多中心研究，包括2016年至2019年在荷兰新诊断为癌症的儿童。在癌症诊断之前被诊断为TPS的儿童被排除在外。筛选工具包括一份检查表，2D和3D摄影系列和数字评估这些由临床遗传学家。如果怀疑TPS，该患者被评估为阳性，并接受常规遗传咨询。主要目的是评估这种新筛查工具的临床价值。在363名患者中，57%(208/363)被评估为阳性。在15％的患者（32/208）中，具有(n=12)或不具有(n=20)3D照片的2D照片系列在阳性评估中是决定性的.在2%(4/208)的阳性评估患者中，一个TPS被诊断出来,在另外2％（4/208）中发现了不确定意义的种系变异。通过常规遗传咨询评估了35名阴性患者作为对照，没有检测到TPS。使用筛选工具，57%的患者被评估为怀疑患有TPS。在临床护理环境中，阴性对照组未发现假阴性结果。观察到的TPS患病率低于预期，由于队列中的选择偏差。
