Presentation: Child with cystic renal disease

A 13-year-old girl presents to her GP with symptoms of polyuria, back pain and fatigue. Previous blood tests revealed renal impairment and resulted in hospital admission. There is no family history of note. Further investigations were performed including a renal ultrasound, which showed bilateral cortico-medullary cysts.

• Testing is recommended for patients with non-syndromic cystic renal disease, for example autosomal recessive polycystic kidney disease (ARPKD) or autosomal dominant polycystic kidney disease (ADPKD) (excluding acquired cystic disease due to chronic or end stage kidney disease), which is either: 
  • clinically not characteristic of ADPKD and an underlying diagnosis would support management;
  • clinically symptomatic (pain, hypertension, haematuria, urinary tract infections) disease presenting before the age of 18; or
  • suggestive of ADPKD and an underlying diagnosis is required to influence management.

• Consult the National Genomic Test Directory. From this link you can access the rare and inherited disease eligibility criteria document for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our Knowledge Hub resource ‘Genomic testing in the devolved nations’.
  • To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed-Off Panels Resource.
• Decide which of the tests best suits the needs of your patient/family. For cystic renal disease, there are a number of available tests including:
  • R193 Cystic renal disease: This indication should be used when a child presents with renal cysts on ultrasound (where acquired or syndromic causes are excluded) or with symptoms before the age of 18, or when a genetic diagnosis is requirement for management. This test includes a whole genome sequencing (WGS) panel.
  • R257 Unexplained young onset end-stage renal disease: This indication should be used for patients up to the age of 36 presenting with unexplained end-stage renal disease where no cause has been identified by clinical assessment, biochemistry, imaging or biopsy. This test includes a WGS panel. See our other resources: ‘Child or young person with unexplained end-stage renal disease’ and ‘Neonate with unexplained end-stage renal disease’.
  • R141 Monogenic diabetes: This indication should be used for patients with suspected renal cysts and diabetes syndrome (RCAD). This test includes whole exome sequencing or a medium-sized gene panel and multiplex ligation-dependent probe amplification (MLPA) or equivalent.
  • R202 Tubulointerstitial kidney disease: This indication is for patients with tubulointerstitial fibrosis with no glomerular lesion and no identifiable cause, often associated with medullary cysts, hyperuricaemia, or gout, if they have a relative with tubulointerstitial kidney disease (TIKD) or unexplained end-stage renal disease. This includes a small gene panel and MLPA. See ‘Adult with unexplained chronic kidney disease‘.
  • R27 Paediatric disorders and R89 Ultra-rare and atypical monogenic disorders should be considered for individuals with complex or syndromic presentations. R27 includes microarray and a WGS ‘super-panel’. R89 includes microarray and WGS panels selected by the requesting clinician. Both tests require authorisation from clinical genetics.
  • R240 Diagnostic testing for known mutation(s): Can be used for a patient who is clinically affected with cystic renal disease if a member of the family already has 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 mutation(s): A predictive (also known as presymptomatic) test for unaffected individuals who have a family member with a known pathogenic or likely pathogenic variant. This test requires authorisation from clinical genetics.
• For WGS-based tests,  including R193, R257, R27, and R89, you will need to:
  • Complete an NHS GMS test order form with details of the affected child (proband) and their parents. Include details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see how to complete a test order form for WGS for support).
  • Complete an NHS GMS record of discussion form for each person being tested. If you are undertaking trio testing of an affected individual and their parents, you will need to complete three forms. See how to complete a record of discussion form for support.
  • Submit parental samples alongside the child’s sample where possible to aid interpretation, especially for the larger WGS panels. Where this is not possible, for example if the child is in care and there is no access to parents, or if one parent is unavailable for testing, the child’s sample may still be submitted.
• For tests that do not include WGS, including R202, R141, R240, R242:
  • Use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms.
  • When testing in children, parental samples may be needed 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.
• These tests are DNA-based, so an EDTA sample (purple-topped tube) is required.

• GeneReviews: Bardet-Biedl Syndrome
• GeneReviews: Nephronophthisis-Related Ciliopathies
• GeneReviews: Polycystic Kidney Disease, Autosomal Dominant
• GeneReviews: Polycystic Kidney Disease, Autosomal Recessive
• Genomics England: NHS Genomic Medicine Service (GMS) signed off panels resource
• KDIGO: Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• NHS England: National Genomic Test Directory
• Orphanet (information about rare diseases and orphan drugs)
• US National Library of Medicine: Polycystic kidney disease

References:

• Hanna C, Iliuta IA, Besse W and others. ‘Cystic Kidney Diseases in Children and Adults: Differences and Gaps in Clinical Management’. Seminars in Nephrology 2023: volume 43, issue 4. DOI: 10.1016/j.semnephrol.2023.151434

For patients

• infoKID (information for parents and carers of children with kidney conditions)
• Kidney Care UK: Polycystic kidney disease
• Kidney Research UK: What is polycystic kidney disease?
• PKD Foundation: What is PKD?
• Polycystic Kidney Disease Charity
• NHS Health A to Z: Autosomal dominant polycystic kidney disease