1373 Rapid exome sequencing for acutely unwell children: experiences from Yorkshire regional genetics service
1373 Rapid exome sequencing for acutely unwell children: experiences from Yorkshire regional genetics service
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第1373章
DOI：
10.1136/archdischild-2021-rcpch.597
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Lerou D
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作者：
Lerou D
儿童和婴儿罕见的单基因疾病很难诊断，但确诊在指导患者治疗和影响临床决策方面具有重要作用。2019年10月1日，通过国家基因组测试目录，在整个英国NHS推出了针对可能患有单基因疾病(R14)的急性不适儿童的国家快速外显子组测序服务。英格兰的所有新生儿重症监护病房(NICU)都可以获得国家R14服务。这项检测的知情同意是至关重要的，因为结果可能会给出不确定或意想不到的信息，包括关于儿童亲生父母的信息。通过R14的快速三重外显子全外显子组测序(WES)使寻求可能影响儿童临床管理的紧急诊断成为可能。目的我们通过审查自R14服务开始以来一年内约克郡区域遗传学服务(YRGS)的所有转诊，对我们地区的R14服务进行了审计和服务评估。方法我们审查了2019年10月1日至2020年9月30日期间从约克郡区域遗传学服务中心到国家委托的埃克塞特基因组实验室的所有R14转诊。我们的数据收集工具能够对患者笔记、电子患者记录以及基因组和其他测试结果进行标准化筛选。收集了患者的人口统计学、临床和表型信息以及基因组结果数据。结果确定了46例患者，其中男性18例(39%)，女性28例(61%)。审查时先证者的中位年龄为20天。热图显示，大多数使用过这项服务的患者都集中在西约克郡。在提出要求时，65%(n=30)的患者在NICU。在50%(n=23)的病例中，新生儿病房要求进行检测。在43%(n=20)的患者中，临床遗传学部门要求进行测试。神经科要求测试的占4%(n=2)，高依赖单位要求测试的占2%(n=1)。申请表格填写完整的占74%(n=34)。在46%(n=21)的病例中，没有记录对测试的同意(通过讨论表格的记录)。埃克塞特基因组实验室从收到样本到发布最终报告的平均周转时间为12.7天(范围为7-25天)。在52%(n=24)的病例中，确定了导致患者症状的遗传原因。在这24个案例中，96%(n=23)导致了管理层的变更。最常见的管理变化是转诊到专科医生(52%；n=12)。结论R14服务严重依赖于新生儿和临床遗传学团队之间的有效合作，因为两个团队都参与了转诊过程。重要的是，我们要改进我们的文件，特别是关于测试同意的文件，并确保申请表在提交之前完全填写完毕。在我们的病例中，超过一半的病例被确定为患者表现的遗传原因；在这些病例中，除一例外，所有病例都影响了患者管理的某些方面。这次审计帮助我们确定了确保在我们地区公平使用R14服务的战略。
BackgroundRare monogenic disorders in children and babies are difficult to diagnose, however establishing the diagnosis plays an important role in informing patient management and influencing clinical decision-making. On 1st October 2019, the National Rapid Exome Sequencing Service for acutely unwell children with a likely monogenic disorder (R14) was introduced across NHS England, via the National Genomic Test Directory. All Neonatal Intensive Care Units (NICUs) in England have access to the national R14 service. Informed consent for this test is essential, as the results may give uncertain or unexpected information, including about a child’s biological parents. Rapid trio Whole Exome Sequencing (WES) via R14 has enabled urgent diagnoses to be sought where this may affect the clinical management of the child.ObjectivesWe undertook an audit and service evaluation of the R14 service in our region by reviewing all referrals to Yorkshire Regional Genetics Service (YRGS) over a one-year period since the commencement of the R14 service.MethodsWe reviewed all R14 referrals from YRGS to the nationally-commissioned Exeter Genomics Lab between 1st October 2019 and 30th September 2020. Our data collection tool enabled a standardised screening of patient notes, electronic patient records and genomic and other test results. Patient demographics, clinical and phenotypic information, and genomic outcome data were collected.Results46 cases were identified; 18 male (39%), 28 female (61%). The median age of the proband at time of review was 20 days. A heat map demonstrated that most patients who had accessed the service were concentrated in West Yorkshire. At the time of request, 65% (n=30) of patients were on NICU. In 50% (n=23), the neonatal unit requested the test. In 43% (n=20), Clinical Genetics requested the test. In 4% (n=2), the test was requested by neurology, and 2% (n=1) by a High Dependency Unit. Request forms were fully complete in 74% (n=34) of cases. In 46% (n=21) of cases, consent for testing (via a record of discussion form) was not documented. The mean turnaround time from receipt of samples by the Exeter Genomics Lab to issuing of final reports was 12.7 days (range 7–25 days). In 52% (n=24) of cases, a genetic cause for the patient’s presentation was identified. Of these 24 cases, 96% (n=23) resulted in a change in management. The most common change in management was referral to a specialist (52%; n=12).ConclusionsThe R14 service for acutely unwell children heavily relies on effective collaboration between Neonatal and Clinical Genetics teams, as both teams are involved in the referral process. It is important that we improve our documentation – particularly around consent for testing - and ensure request forms are fully completed before submission. In over half of our cases, a genetic cause for the patient’s presentation was identified; in all but one of these cases, this affected some aspect of patient management. This audit has helped us to identify strategies to ensure equitable access to the R14 service across our region.