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Review
. 2017 Nov 3;43(1):100.
doi: 10.1186/s13052-017-0418-0.

Intersociety policy statement on the use of whole-exome sequencing in the critically ill newborn infant

Alessandro Borghesi  1 , Maria Antonietta Mencarelli  2 , Luigi Memo  3 , Giovanni Battista Ferrero  4 , Andrea Bartuli  5 , Maurizio Genuardi  6 , Mauro Stronati  7 , Alberto Villani  8 , Alessandra Renieri  2   9 , Giovanni Corsello  10 ; their respective Scientific Societies
Collaborators, Affiliations
Review

Intersociety policy statement on the use of whole-exome sequencing in the critically ill newborn infant

Alessandro Borghesi et al. Ital J Pediatr. .

Abstract

The rapid advancement of next-generation sequencing (NGS) technology and the decrease in costs for whole-exome sequencing (WES) and whole-genome sequening (WGS), has prompted its clinical application in several fields of medicine. Currently, there are no specific guidelines for the use of NGS in the field of neonatal medicine and in the diagnosis of genetic diseases in critically ill newborn infants. As a consequence, NGS may be underused with reduced diagnostic success rate, or overused, with increased costs for the healthcare system. Most genetic diseases may be already expressed during the neonatal age, but their identification may be complicated by nonspecific presentation, especially in the setting of critical clinical conditions. The differential diagnosis process in the neonatal intensive care unit (NICU) may be time-consuming, uncomfortable for the patient due to repeated sampling, and ineffective in reaching a molecular diagnosis during NICU stay. Serial gene sequencing (Sanger sequencing) may be successful only for conditions for which the clinical phenotype strongly suggests a diagnostic hypothesis and for genetically homogeneous diseases. Newborn screenings with Guthrie cards, which vary from country to country, are designed to only test for a few dozen genetic diseases out of the more than 6000 diseases for which a genetic characterization is available. The use of WES in selected cases in the NICU may overcome these issues. We present an intersociety document that aims to define the best indications for the use of WES in different clinical scenarios in the NICU. We propose that WES is used in the NICU for critically ill newborn infants when an early diagnosis is desirable to guide the clinical management during NICU stay, when a strong hypothesis cannot be formulated based on the clinical phenotype or the disease is genetically heterogeneous, and when specific non-genetic laboratory tests are not available. The use of WES may reduce the time for diagnosis in infants during NICU stay and may eventually result in cost-effectiveness.

Keywords: Diagnosis; Genetic; Genome; Mendelian; NICU; Neonatal intensive care unit; Neonate; WES; WGS; Whole-exome sequencing.

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Conflict of interest statement

Authors’ information

The respective Scientific Societies of the authors of this paper are as follows: Italian Society of Pediatrics (SIP), Italian Society of Neonatology (SIN), Italian Society of Pediatric Genetic Diseases and Congenital Disabilities (SIMGePed), and Italian Society of Human Genetics (SIGU).

Ethics approval and consent to participate

Not applicable.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Diagnostic algorithm for genetic testing in the critically ill newborn infant
See this image and copyright information in PMC

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