West Midlands Clinical Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Edgbaston, UK.
Centre for Public Health, Queen's University Belfast, Belfast, UK.
Ultrasound Obstet Gynecol. 2024 Sep;64(3):381-387. doi: 10.1002/uog.27647. Epub 2024 Aug 12.
In the West Midlands regional genetics service, cases of perinatal death with a possible genetic diagnosis are evaluated by the perinatal pathology genetic multidisciplinary team (MDT). The MDT assesses autopsy findings and suggests appropriate genomic assessment. The objective of this retrospective service evaluation was to determine the clinical utility of the MDT in assessing perinatal deaths associated with structural anomaly. This is the first evaluation since the introduction of whole-genome and whole-exome sequencing in routine clinical care.
This was a retrospective service evaluation including all cases of perinatal death with an associated structural anomaly and suspected genetic etiology that underwent perinatal MDT assessment between January and December 2021. All cases received a full or partial postmortem examination and at least a chromosomal microarray analysis. Demographic characteristics, phenotype, genotype, MDT recommendations, diagnoses, outcomes and impact of postmortem analysis and genetic testing data were collected from patient case notes.
Overall, 123 cases were discussed at the MDT meetings in 2021. Genetic evaluation was recommended in 84 cases and accepted in 64 cases. A range of genetic tests were requested according to indication and availability. Thirty diagnoses were made in 29 cases from 26 unrelated families. The diagnostic yield was 24% (29/123) in all cases or 45% (29/64) in cases with a suspected genetic diagnosis who underwent genetic testing. Postmortem examination provided clinically actionable phenotypic data in 79% of cases. A genetic diagnosis enabled accurate recurrence risk counseling and provision of appropriate follow-up, including prenatal testing and preimplantation diagnosis for patients with inherited conditions.
Genomic testing was a clinically useful addition to (but not a substitute for) postmortem examination in cases of perinatal death associated with structural anomaly. The MDT approach helped assess cases and plan appropriate follow-up. Expedited whole-genome sequencing or panel-agnostic analysis were most appropriate for heterogeneous presentations. This broad approach can also expand knowledge of prenatal phenotypes and detect novel disease genes, and should be a priority in future research. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
在西米德兰兹地区遗传服务中，由围产期病理学遗传多学科团队（MDT）评估具有潜在遗传诊断的围产期死亡病例。MDT 评估尸检结果并建议进行适当的基因组评估。本回顾性服务评估的目的是确定 MDT 在评估与结构异常相关的围产儿死亡中的临床应用价值。这是自全基因组和全外显子组测序引入常规临床护理以来的首次评估。
这是一项回顾性服务评估，纳入了 2021 年 1 月至 12 月期间接受围产期 MDT 评估的所有具有相关结构异常和疑似遗传病因的围产儿死亡病例。所有病例均接受了全面或部分尸检检查，至少进行了染色体微阵列分析。从患者病历中收集人口统计学特征、表型、基因型、MDT 建议、诊断、结局以及尸检分析和遗传检测数据的影响。
2021 年，MDT 会议共讨论了 123 例病例。建议进行基因评估 84 例，接受 64 例。根据适应证和可用性要求，请求了一系列基因检测。26 个无关家庭中有 29 例的 30 个诊断。所有病例的诊断率为 24%（29/123），疑似遗传诊断且接受基因检测的病例的诊断率为 45%（29/64）。尸检检查提供了 79%病例具有临床意义的表型数据。基因诊断可准确进行遗传风险咨询，并为有遗传疾病的患者提供适当的随访，包括产前检查和植入前诊断。
基因组检测是结构异常相关围产儿死亡病例尸检检查的一种有用的临床补充（但不能替代）。MDT 方法有助于评估病例并计划适当的随访。加快全基因组测序或无探针分析最适合异质性表现。这种广泛的方法还可以扩展产前表型知识并检测新的疾病基因，应成为未来研究的重点。
