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

Authors :
Maayan Kagan
Rotem Semo-Oz
Yishay Ben Moshe
Danit Atias-Varon
Irit Tirosh
Michal Stern-Zimmer
Aviva Eliyahu
Annick Raas-Rothschild
Maayan Bivas
Omer Shlomovitz
Odelia Chorin
Rachel Rock
Michal Tzadok
Bruria Ben-Zeev
Gali Heimer
Yoav Bolkier
Noah Gruber
Adi Dagan
Bat El Bar Aluma
Itai M. Pessach
Gideon Rechavi
Ortal Barel
Ben Pode-Shakked
Yair Anikster
Asaf Vivante
Source :
Frontiers in Genetics, Vol 13 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

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.

Details

Language :
English
ISSN :
16648021
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Genetics
Publication Type :
Academic Journal
Accession number :
edsdoj.5ffe107900c941c4ab532f5edb295397
Document Type :
article
Full Text :
https://doi.org/10.3389/fgene.2022.1018062