Kagan Maayan, Semo-Oz Rotem, Ben Moshe Yishay, Atias-Varon Danit, Tirosh Irit, Stern-Zimmer Michal, Eliyahu Aviva, Raas-Rothschild Annick, Bivas Maayan, Shlomovitz Omer, Chorin Odelia, Rock Rachel, Tzadok Michal, Ben-Zeev Bruria, Heimer Gali, Bolkier Yoav, Gruber Noah, Dagan Adi, Bar Aluma Bat El, Pessach Itai M, Rechavi Gideon, Barel Ortal, Pode-Shakked Ben, Anikster Yair, Vivante Asaf
Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Front Genet. 2023 Jan 9;13:1018062. doi: 10.3389/fgene.2022.1018062. eCollection 2022.
Genetic conditions contribute a significant portion of disease etiologies in children admitted to general pediatric wards worldwide. While exome sequencing (ES) has improved clinical diagnosis and management over a variety of pediatric subspecialties, it is not yet routinely used by general pediatric hospitalists. We aim to investigate the impact of exome sequencing in sequencing-naive children suspected of having monogenic disorders while receiving inpatient care. We prospectively employed exome sequencing in children admitted to the general pediatric inpatient service at a large tertiary medical center in Israel. Genetic analysis was triggered by general and/or subspecialist pediatricians who were part of the primary inpatient team. We determined the diagnostic yield among children who were referred for exome sequencing and observed the effects of genetic diagnosis on medical care. A total of fifty probands were evaluated and exome sequenced during the study period. The most common phenotypes included were neurodevelopmental (56%), gastrointestinal (34%), and congenital cardiac anomalies (24%). A molecular diagnosis was reached in 38% of patients. Among seven patients (37%), the molecular genetic diagnosis influenced subsequent clinical management already during admission or shortly following discharge. We identified a significant fraction of genetic etiologies among undiagnosed children admitted to the general pediatric ward. Our results support that early application of exome sequencing may be maximized by pediatric hospitalists' high index of suspicion for an underlying genetic etiology, prompting an in-house genetic evaluation. This framework should include a multidisciplinary co-management approach of the primary care team working alongside with subspecialties, geneticists and bioinformaticians.
在全球范围内，入住普通儿科病房的儿童中，遗传因素在疾病病因中占很大比例。虽然外显子组测序（ES）已改善了多种儿科亚专业的临床诊断和管理，但普通儿科住院医师尚未常规使用。我们旨在研究外显子组测序对在住院治疗期间疑似患有单基因疾病的未进行过测序的儿童的影响。我们前瞻性地对以色列一家大型三级医疗中心普通儿科住院部收治的儿童采用了外显子组测序。遗传分析由作为主要住院团队一部分的普通儿科医生和/或儿科专科医生发起。我们确定了接受外显子组测序的儿童的诊断率，并观察了基因诊断对医疗护理的影响。在研究期间，共评估了50名先证者并进行了外显子组测序。最常见的表型包括神经发育（56%）、胃肠道（34%）和先天性心脏异常（24%）。38%的患者获得了分子诊断。在7名患者（37%）中，分子遗传学诊断在入院期间或出院后不久就影响了后续的临床管理。我们在入住普通儿科病房的未确诊儿童中发现了很大一部分遗传病因。我们的结果支持，儿科住院医师对潜在遗传病因的高度怀疑可能会促使进行内部基因评估，从而使外显子组测序的早期应用最大化。这个框架应包括初级护理团队与各亚专业、遗传学家和生物信息学家共同进行多学科管理的方法。
