Strategies in Rapid Genetic Diagnostics of Critically Ill Children: Experiences From a Dutch University Hospital

Genetic disorders are a substantial cause of infant morbidity and mortality and are frequently suspected in neonatal intensive care units. Non-specific clinical presentation or limitations to physical examination can result in a plethora of genetic testing techniques, without clear strategies on tes...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in pediatrics Vol. 9; p. 600556
Main Authors:	Imafidon, Miriam E, Sikkema-Raddatz, Birgit, Abbott, Kristin M, Meems-Veldhuis, Martine T, Swertz, Morris A, van der Velde, K Joeri, Beunders, Gea, Bos, Dennis K, Knoers, Nine V A M, Kerstjens-Frederikse, Wilhelmina S, van Diemen, Cleo C
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 31-05-2021
Subjects:	copy number variation genetic diagnostics genetic disease neonatal intensive care (unit) next generation sequencing Pediatrics neonatal intensive care (unit) copy number variation genetic diagnostics genetic disease next generation sequencing
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Genetic disorders are a substantial cause of infant morbidity and mortality and are frequently suspected in neonatal intensive care units. Non-specific clinical presentation or limitations to physical examination can result in a plethora of genetic testing techniques, without clear strategies on test ordering. Here, we review our 2-years experiences of rapid genetic testing of NICU patients in order to provide such recommendations. We retrospectively included all patients admitted to the NICU who received clinical genetic consultation and genetic testing in our University hospital. We documented reasons for referral for genetic consultation, presenting phenotypes, differential diagnoses, genetic testing requested and their outcomes, as well as the consequences of each (rapid) genetic diagnostic approach. We calculated diagnostic yield and turnaround times (TATs). Of 171 included infants that received genetic consultation 140 underwent genetic testing. As a result of testing as first tier, 13/14 patients received a genetic diagnosis from QF-PCR; 14/115 from SNP-array; 12/89 from NGS testing, of whom 4/46 were diagnosed with a small gene panel and 8/43 with a large OMIM-morbid based gene panel. Subsequent secondary or tertiary analysis and/or additional testing resulted in five more diagnoses. TATs ranged from 1 day (QF-PCR) to a median of 14 for NGS and SNP-array testing, with increasing TAT in particular when many consecutive tests were performed. Incidental findings were detected in 5/140 tested patients (3.6%). We recommend implementing a broad NGS gene panel in combination with CNV calling as the first tier of genetic testing for NICU patients given the often unspecific phenotypes of ill infants and the high yield of this large panel.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Neonatology, a section of the journal Frontiers in Pediatrics Edited by: Pankaj Agrawal, Harvard University, United States These authors have contributed equally to this work Reviewed by: Linda De Vries, Leiden University Medical Center, Netherlands; Zornitza Stark, Royal Children's Hospital, Australia
ISSN:	2296-2360 2296-2360
DOI:	10.3389/fped.2021.600556