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Paediatrics

Presentation: Neonate with unexplained end-stage renal disease

Over a third of children presenting with unexplained end-stage renal disease may have an underlying monogenic cause. Establishing a genetic diagnosis can inform management, treatment and genomic counselling decisions.

Example clinical scenario

A one-day-old baby on the neonatal unit develops bilious vomiting and abdominal distension in the absence of passing meconium. Bilateral hydronephrosis and an enlarged bladder were identified antenatally. Blood tests show rising urea and creatinine. A contrast study shows impaired peristalsis and microcolon, and an abdominal ultrasound reveals a large, dilated non-obstructed urinary bladder.

When to consider genomic testing

  • No cause has been identified by clinical assessment, biochemistry, imaging or renal biopsy.
  • Unexplained end-stage renal disease associated with:
    • atypical growth patterns (overgrowth, asymmetric growth);
    • extra-renal features (for example ocular, hearing loss, neurological, gastrointestinal);
    • a family history of a renal condition or syndrome;
    • dysmorphic facial features or congenital malformations (where targeted testing is not possible); and/or
    • a syndrome, or atypical growth, with intellectual disability or developmental delay.
  • Semi-rapid testing can be requested in acutely unwell children or adults where monogenic young onset end-stage renal disease is considered highly likely to be the primary cause of the phenotype. Cases should meet the standard eligibility criteria for test R257 in the National Genomic Test Directory (see more information below). The clinical team should establish that:
    • testing will or could provide an immediate change to treatment or clinical management of the patient, for example by informing decisions about renal transplant, therapeutic intervention or prenatal testing for an ongoing at risk pregnancy; and
    • the patient is either not eligible for the R14 pathway for acutely unwell children or rapid R257 testing is considered to be the more appropriate test.

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/family. For end stage renal diseases, there are a number of available panels including:
    • R257 Unexplained young onset end-stage renal disease: This indication should be considered for patients under 36 years of age presenting with unexplained end-stage renal disease where no cause has been identified by clinical assessment, biochemistry, imaging or biopsy. This test is carried out using whole genome sequencing (WGS).
  • If there are additional features that suggest a particular diagnosis, consider the following tests:
    • R199 Congenital anomalies of the kidney and urinary tract – familial: This indication should be used if there are clinically significant non-syndromic congenital anomalies of the kidney and urinary tract (CAKUT) and the patient has a first-degree relative with CAKUT or unexplained end-stage renal disease. This test uses microarray. See Presentation: Child with an ectopic kidney.
    • R27 Paediatric disorders and R89 Ultra-rare and atypical monogenic disorders: These indications should be considered for individuals with complex or syndromic presentations. R89 includes microarray and WGS panels selected by the requesting clinician. 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.
    • R240 Diagnostic testing for known variant(s): This indication is suitable for those who are clinically affected with renal disease and have a family member with a known pathogenic or likely pathogenic variant. In this situation, the laboratory will only test for the known familial variant.
    • R242 Predictive testing for known familial variant(s): This indication is for a predictive (also known as presymtomatic) test for those who are unaffected but have a relative with a known pathogenic or likely pathogenic variant. This test requires authorisation from clinical genetics.
  • For tests that do not include WGS, including R199, R240 and R242:
  • For tests that are undertaken using WGS, including R257, R27 and R89, you will need to:
  • When testing in children, parental samples may be helpful for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
  • 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

  • MMIHS (information and support for people affected by megacystis microcolon intestinal hypoperistalsis syndrome)
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  • Last reviewed: 25/02/2026
  • Next review due: 25/02/2027
  • Authors: Dr Felicity Beal
  • Reviewers: Dr Danielle Bogue, Professor Richard Sandford, Professor John A Sayer

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