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

Miriam E. Imafidon, Birgit Sikkema-Raddatz, Kristin M. Abbott, Martine T. Meems-Veldhuis, Morris A. Swertz, K. Joeri van der Velde, Gea Beunders, Dennis K. Bos, Nine V. A. M. Knoers, Wilhelmina S. Kerstjens-Frederikse, Cleo C. van Diemen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: 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.

Methods: 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).

Results: 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%).

Conclusion: 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.

Original languageEnglish
Article number600556
Number of pages15
JournalFrontiers in Pediatrics
Publication statusPublished - 31-May-2021


  • neonatal intensive care (unit)
  • next generation sequencing
  • genetic diagnostics
  • copy number variation
  • genetic disease

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