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Fifteen-minute consultation: The efficient investigation of infantile and childhood epileptic encephalopathies in the era of modern genomics
  1. Luke Daniel Perry1,
  2. Sarah Louise Hogg2,
  3. Sarah Bowdin3,
  4. Gautam Ambegaonkar4,
  5. Alasdair PJ Parker4
  1. 1 Developmental Neurosciences, University College London, Great Ormond Street Institute of Child Health, London, UK
  2. 2 Biochemical Genetics Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  3. 3 Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  4. 4 Paediatric Neurology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  1. Correspondence to Dr Luke Daniel Perry, Developmental Neurosciences, University College London, Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; luke.perry{at}gosh.nhs.uk

Abstract

The investigation of children presenting with infantile and childhood epileptic encephalopathies (ICEE) is challenging due to diverse aetiologies, overlapping phenotypes and the relatively low diagnostic yield of MRI, electroencephalography (EEG) and biochemical investigations. Careful history and thorough examination remain essential as these may identify an acquired cause or indicate more targeted investigation for a genetic disorder. Whole exome sequencing (WES) with analysis of a panel of candidate epilepsy genes has increased the diagnostic yield. Whole genome sequencing (WGS), particularly as a trio with both parents’ DNA, is likely to supersede WES. Modern genomic investigation impacts on the timing and necessity of other testing. We propose a structured approach for children presenting with ICEE where there is diagnostic uncertainty, emphasising the importance of WGS or, if unavailable, WES early in the investigative process. We note the importance of expert review of all investigations, including radiology, neurophysiology and biochemistry, to confirm the technique used was appropriate as well as the results. It is essential to counsel families on the risks associated with the procedures, the yield of the procedures, findings that are difficult to interpret and implication of ‘negative’ results. Where children remain without a diagnosis despite comprehensive investigation, we note the importance of ongoing multidisciplinary care.

  • neurology
  • genetics
  • biochemistry

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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