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Paediatrics

Presentation: Child with recurrent chest infections

Post-infection respiratory symptoms (especially cough) can last up to 25 days, but prolonged/daily cough (particularly if productive) for ≥4 weeks and/or ≥3 episodes of bronchitis/bronchiolitis/pneumonia per year warrant investigations and genomic causes of recurrent lower respiratory tract infections should be considered.

Example clinical scenario

A four-year-old boy is referred to paediatrics from primary care with recurrent lower respiratory tract infections (fever, productive cough and occasional wheeze), requiring oral antibiotics roughly every six to eight weeks since he was 20 months old. His preventer inhaler has minimal effect.

He was born at 37 weeks’ gestation with no neonatal complications. Height and weight are between the 9th–25th centiles. There are no signs of reflux or aspiration. There are scattered crackles on auscultation, with no digital clubbing.

When to consider genomic testing

Cystic fibrosis

Diagnostic testing for cystic fibrosis (CF) should be considered in childhood in the scenarios below.

  • Where there is clinical suspicion of CF in a child (for example, recurrent chest infections, failure to thrive, fat malabsorption and neonatal history of meconium ileus); and
    • a not normal sweat test exists, which has been performed in a recognised experienced test centre/laboratory (that is, sweat chloride ≥30mM with sufficient sweat obtained); or
    • an additional urgent prenatal situation has taken place for the parents or for a close relative, but urgent sweat testing is not accessible.
  • Idiopathic chronic pancreatitis with exocrine dysfunction (fat malabsorption) with other obvious and acquired causes excluded; and
    • a not normal sweat test exists, which was performed in a recognised experienced test centre/laboratory (that is, sweat chloride ≥30mM with sufficient sweat obtained); or
    • sweat testing is not practical and all other causes have been excluded.
  • Fetal echogenic bowel ‘as bright as bone’ on the second trimester scan, or dilated fetal bowel on the second or third trimester scan with echogenic bowel as bright as bone; and
    • both parents are unavailable for carrier testing (if both parents are available, CF carrier testing should be used instead of an invasive prenatal test); and
    • other, more common causes have been excluded (for example, intrauterine growth restriction, placental failure, earlier bleeding, infection and raised aneuploidy markers).

In the UK, CF is typically identified during newborn blood spot test screening, though individuals who are missed (such as those born outside of the UK where routine screening is not available) may present in childhood.

Primary immunodeficiency

Primary immunodeficiency diagnostic testing should be considered if suspected or diagnosed by a consultant immunologist.

Indications include patients with any of the International Union of Immunological Societies’ (IUIS) categories of primary immunodeficiency:

  • combined immunodeficiency, with or without associated features and abnormal T cell numbers or function. This may include abnormal naïve T cells, T-cell receptor excision circles (TRECs), repertoire, proliferations (for example, phytohaemagglutinin (PHA)), reversed CD4/8 ratio or increased gamma delta T cells;
  • predominantly antibody deficiencies with low or absent vaccine responses;
  • diseases of immune dysregulation, including haemophagocytic lymphohistiocytosis (HLH);
  • congenital defects of phagocyte number, function or both. This should be evidenced by low phagocytic 204 numbers and/or abnormal dihydrorhodamine (DHR)/nitroblue tetrazolium (NBT)/phagocytosis/L-selectin shedding, CD11a,b,c or CD18, or abnormal migration or adhesion;
  • defects in intrinsic and innate immunity;
  • autoinflammatory disorders;
  • complement deficiencies with abnormal complement function; or
  • bone marrow failure.

Testing under these criteria would also include young children with inflammatory bowel disease: defined as bloody diarrhoea, severe failure to thrive and severe intestinal inflammation with histology consistent with chronic inflammatory intestinal pathology, of onset under six years of age.

The 2024 update of IUIS phenotypic classification of human inborn errors of immunity contains a decision tree to aid navigation through the different classification categories.

For more information see Presentation: Patient presenting with severe, recurrent, persistent and/or unusual infections.

Respiratory ciliopathies including non-CF bronchiectasis

Diagnostic testing in childhood for respiratory ciliopathies (see Lucas JS and others) including non-CF bronchiectasis should be considered in the following scenarios:

  • neonatal presentation with at least one of:
    • situs inversus plus lower airway or nasal symptoms;
    • persistent respiratory distress where other causes have been excluded; or
    • persistent rhinorrhea and cough where other causes have been excluded;
  • children with at least one of:
    • persistent life-long wet cough (CF excluded);
    • unexplained bronchiectasis (CF excluded); or
    • serous otitis media in association with lower and upper airway symptoms.

What do you need to do?

  • Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
  • Decide which of the panels best suits the needs of your patient or family.
    • To investigate children where the principle clinical concern is recurrent lower respiratory tract infections, there are a number of available panels, including:
      • R184 Cystic fibrosis diagnostic test: This is targeted variant testing and multiplex ligation-dependent probe amplification (MLPA) or equivalent;
      • R15 Primary immunodeficiency or monogenic inflammatory bowel disease: This is typically whole genome sequencing (WGS) though whole exome sequencing (WES) can be conducted if semi-urgent testing is required;
      • R189 Respiratory ciliopathies including non-CF bronchiectasis: This is WES or medium panel.
    • For children with wider presentations (for example, growth patterns outside of the normal range, other health concerns, developmental delay/intellectual disability and/or those with distinctive features from their family), broader testing (as well as those listed above) may be more appropriate:
      • R27 Paediatric disorders: R27 is an amalgamation of over 10 panels of genes known to be associated with a broad range of paediatric developmental disorders. It may now be ordered directly by paediatricians, though a discussion with clinical genetics services may be beneficial.
  • For tests that do not include WGS, including R184 and R189:
    • you can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms; and
    • parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
  • For tests that are undertaken using WGS, including R15 and R27, you will need to:
  • Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
  • If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 17/04/2026
  • Next review due: 17/04/2028
  • Authors: Dr Norrice Liu
  • Reviewers: Dr Joanna Kennedy, Dr Eleanor Hay

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