Frontiers in Genetics (Jan 2023)

Clinical impact of exome sequencing in the setting of a general pediatric ward for hospitalized children with suspected genetic disorders

  • Maayan Kagan,
  • Maayan Kagan,
  • Maayan Kagan,
  • Rotem Semo-Oz,
  • Rotem Semo-Oz,
  • Rotem Semo-Oz,
  • Yishay Ben Moshe,
  • Yishay Ben Moshe,
  • Danit Atias-Varon,
  • Irit Tirosh,
  • Irit Tirosh,
  • Irit Tirosh,
  • Michal Stern-Zimmer,
  • Michal Stern-Zimmer,
  • Aviva Eliyahu,
  • Aviva Eliyahu,
  • Annick Raas-Rothschild,
  • Annick Raas-Rothschild,
  • Maayan Bivas,
  • Maayan Bivas,
  • Omer Shlomovitz,
  • Omer Shlomovitz,
  • Odelia Chorin,
  • Odelia Chorin,
  • Odelia Chorin,
  • Rachel Rock,
  • Rachel Rock,
  • Rachel Rock,
  • Michal Tzadok,
  • Michal Tzadok,
  • Bruria Ben-Zeev,
  • Bruria Ben-Zeev,
  • Gali Heimer,
  • Gali Heimer,
  • Gali Heimer,
  • Yoav Bolkier,
  • Yoav Bolkier,
  • Noah Gruber,
  • Noah Gruber,
  • Noah Gruber,
  • Adi Dagan,
  • Adi Dagan,
  • Adi Dagan,
  • Bat El Bar Aluma,
  • Bat El Bar Aluma,
  • Bat El Bar Aluma,
  • Itai M. Pessach,
  • Itai M. Pessach,
  • Itai M. Pessach,
  • Gideon Rechavi,
  • Gideon Rechavi,
  • Gideon Rechavi,
  • Ortal Barel,
  • Ortal Barel,
  • Ortal Barel,
  • Ben Pode-Shakked,
  • Ben Pode-Shakked,
  • Ben Pode-Shakked,
  • Ben Pode-Shakked,
  • Yair Anikster,
  • Yair Anikster,
  • Yair Anikster,
  • Asaf Vivante,
  • Asaf Vivante,
  • Asaf Vivante,
  • Asaf Vivante

DOI
https://doi.org/10.3389/fgene.2022.1018062
Journal volume & issue
Vol. 13

Abstract

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Background: 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.Methods: 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.Results: 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.Conclusion: 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.

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