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Should next-generation sequencing be considered as a first-line genetic investigation for children with early developmental impairment?
  1. Frederica Sarantis1,
  2. Aisosa Osas Guobadia2,
  3. Marwa A Bebars3,
  4. Rachana Varma4,
  5. Jonathon A A Holland5,
  6. Thiloka Ratnaike2,6
  1. 1East and North Hertfordshire NHS Trust, Stevenage, UK
  2. 2Paediatrics, East Suffolk and North Essex NHS Foundation Trust, Colchester, UK
  3. 3Princess Alexandra Hospital NHS Trust, Harlow, UK
  4. 4Norfolk and Norwich University Hospital NHS Trust, Norwich, UK
  5. 5Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK
  6. 6Paediatrics, University of Cambridge, Cambridge, UK
  1. Correspondence to Dr Frederica Sarantis; frederica.sarantis{at}nhs.net

https://doi.org/10.1136/archdischild-2024-327752

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    Scenario

    You see a 3-year-old boy in the Community Paediatrics clinic, referred by their health visitor due to concerns about early developmental impairment (EDI). EDI, also known as global developmental delay, is defined as noticeable delay in achieving developmental milestones in at least two domains in children under 5 years of age. On review, the child’s parents explain that he was born at term following an uncomplicated pregnancy. There were no concerns in the immediate postnatal period apart from some initial feeding issues related to difficulty latching. However, he was noted to be slow in achieving his milestones such as walking without support (at 17 months of age), and he is still not talking short sentences. There are no obvious concerns on general physical examination. Following a Schedule of Growing Skill assessment, you feel the child has a moderate EDI. You are aware that genetic tests are included among the initial investigations in your region, but you are not clear which test is the most appropriate at this early stage—microarray or next-generation sequencing (NGS) with whole exome sequencing (WES) or whole genome sequencing (WGS)?

    Structured clinical question

    In a preschool-aged child with moderate EDI, which genetic test—microarray, WES or WGS—is most appropriate as a first-line genetic investigation?

    Search

    A literature search was undertaken in April 2024 using PubMed with the search terms: “developmental disabilities/diagnosis” [MeSH term] AND “child” [MeSH term] AND “investigation” AND “genetic”, published 2013–2023 inclusive. Inclusion criteria were that the article must discuss investigations of EDI and compare microarray to WES or WGS. Papers were excluded if they were case reports, guidelines or expert opinion.

    The search returned 71 articles, which were screened for relevance by title and abstract returning 39 articles. The full-text articles were independently reviewed (by FS, AOG, MAB) and three articles met the inclusion criteria. An additional meta-analysis found …

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    Footnotes

    • X @M.bebars, @LankanMiller

    • Contributors TR, JAAH and RV designed the project. FS, AOG and MAB undertook the literature review. FS wrote the manuscript with input from all co-authors. TR is the guarantor.

    • Funding JAAH is funded by an Action Medical Research and British Paediatric Neurology Association Research Training Fellowship. This Fellowship has not specifically supported the manuscript and neither Action Medical Research or the British Paediatric Neurology Association have been involved in writing the manuscript.

    • Competing interests JAAH is funded by an Action Medical Research and British Paediatric Neurology Association Research Training Fellowship. FS, AOG, MAB, RV and TR confirm that they have no conflicting interests.

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