Clinical utility of exome sequencing in infantile heart failure

Genetics in Medicine volume 22, pages423–426(2020)Cite this article

Abstract

Purpose

Pediatric cardiomyopathy is rare, has a broad differential diagnosis, results in high morbidity and mortality, and has suboptimal diagnostic yield using next-generation sequencing panels. Exome sequencing has reported diagnostic yields ranging from 30% to 57% for neonates in intensive care units. We aimed to characterize the clinical utility of exome sequencing in infantile heart failure.

Methods

Infants diagnosed with acute heart failure prior to 1 year old over a period of 34 months at a large tertiary children’s hospital were recruited. Demographic and diagnostic information was obtained from medical records. Fifteen eligible patients were enrolled.

Results

Dilated cardiomyopathy was the predominant cardiac diagnosis, seen in 60% of patients. A molecular diagnosis was identified in 66.7% of patients (10/15). Of those diagnoses, 70% would not have been detected using multigene next-generation sequencing panels focused on cardiomyopathy or arrhythmia disease genes. Genetic testing changed medical decision-making in 53% of all cases and 80% of positive cases, and was especially beneficial when testing was expedited.

Conclusion

Given the broad differential diagnosis and critical status of infants with heart failure, rapid exome sequencing provides timely diagnoses, changes medical management, and should be the first-tier molecular test.

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Fig. 1: Patient characteristics.

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Author information

Affiliations

  1. Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Alyssa Ritter MS CGC & Rebecca C. Ahrens-Nicklas MD PhD

  2. Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Alyssa Ritter MS CGC, Justin H. Berger MD PhD & Kimberly Lin MD

  3. Individualized Medical Genetic Center, Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Emma Bedoukian MS CGC, Christopher Gray MS CGC, Ian Krantz MD, Kosuke Izumi MD PhD, Jacqueline Leonard MS CGC, Livija Medne MS CGC & Cara Skraban MD

  4. GeneDx, Inc, Gaithersburg, MD, USA

    Deborah Copenheaver MS CGC, Jane Juusola PhD FACMG & Sandra Yang MS CGC

  5. Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Avni Santani PhD

Authors
  1. Alyssa Ritter MS CGC
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  2. Emma Bedoukian MS CGC
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  3. Justin H. Berger MD PhD
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  4. Deborah Copenheaver MS CGC
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  5. Christopher Gray MS CGC
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  6. Ian Krantz MD
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  7. Kosuke Izumi MD PhD
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  8. Jane Juusola PhD FACMG
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  9. Jacqueline Leonard MS CGC
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  10. Kimberly Lin MD
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  11. Livija Medne MS CGC
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  12. Avni Santani PhD
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  13. Cara Skraban MD
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  14. Sandra Yang MS CGC
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  15. Rebecca C. Ahrens-Nicklas MD PhD
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Corresponding author

Correspondence to Rebecca C. Ahrens-Nicklas MD PhD.

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Disclosure

J.J., D.C. and S.Y. are employees of GeneDx, Inc. The other authors declare no conflicts of interest.

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Ritter, A., Bedoukian, E., Berger, J.H. et al. Clinical utility of exome sequencing in infantile heart failure. Genet Med 22, 423–426 (2020). https://doi.org/10.1038/s41436-019-0654-3

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Keywords

  • exome sequencing
  • heart failure
  • cardiomyopathy
  • pediatric
  • clinical utility

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