AUTHOR=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
TITLE=Clinical impact of exome sequencing in the setting of a general pediatric ward for hospitalized children with suspected genetic disorders
JOURNAL=Frontiers in Genetics
VOLUME=13
YEAR=2023
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1018062
DOI=10.3389/fgene.2022.1018062
ISSN=1664-8021
ABSTRACT=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.