Presentation: Adult with unexpected finding of multiple kidney cysts

A 68-year-old man has been found to have multiple kidney cysts during an ultrasound scan for symptoms of biliary colic. He has no personal or family history of kidney disease but had hypertension for nine years. The kidneys were slightly enlarged but no liver cysts were identified.

Genomic testing should be considered in patients with non-syndromic cystic renal disease (excluding acquired cystic disease due to chronic or end-stage kidney disease) in the following instances:

• When the disease is not clinically characteristic of autosomal dominant polycystic kidney disease (ADPKD) and underlying diagnosis is required for management purposes, for example determining suitability of tolvaptan therapy, referral for preimplantation genetic testing for monogenic conditions (PGT-M) or referring a family member for predictive (also known as presymptomatic) testing.
• When clinically symptomatic disease has presented in the patient before the age of 18.

Where a clinical diagnosis of ADPKD has been made and genetic diagnosis is required to influence management, for example to select disease-specific therapies, refer for PGT-M or for living-related donor assessment.

• Consult the National Genomic Test Directory. 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 how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• 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 tests best suits the needs of your patient/family:
  • R193 Cystic renal disease: This indication uses whole genome sequencing (WGS) to analyse a large panel of genes associated with kidney cysts and should be used for patients who fall into the categories detailed above.
  • R27 Paediatric disorders may be considered for individuals, including adults, with complex or syndromic presentations. R27 includes analysis of the chromosomes and single genes. It is an amalgamation of over 10 panels of genes known to be associated with a broad range of paediatric developmental disorders. For adult patients a discussion with clinical genetics services is likely to be required.
  • R240 Diagnostic testing for known mutation(s): This indication can be used when a patient 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): This is a predictive test to be used for unaffected individuals where a pathogenic or likely pathogenic variant has already been identified in a relative. This test can only be requested by clinical genetics.
• For tests that are undertaken using WGS, including R193 and R27 you will need to:
  • complete an NHS GMS test order form with details of the affected individual (proband) and their parents where available, including 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); and
  • complete an NHS GMS record of discussion (RoD) form for each person being tested – for example if you are undertaking trio testing of an affected individual and their parents, you will need to complete three RoD forms (see How to complete a RoD form for support).
• For tests that do not include WGS, including R240 and R242:
  •  you can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms.
• 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.

For patients

• GeneReviews: Autosomal dominant polycystic kidney disease
• 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)
• MedlinePlus: Polycystic kidney disease
• NHS England: National Genomic Test Directory
• Orphanet (information about rare diseases and orphan drugs)

For patients

• Kidney Care UK: Autosomal dominant polycystic kidney disease (ADPKD)
• Kidney Research UK: What is polycystic kidney disease? 
• NHS Health A to Z: Autosomal dominant polycystic kidney disease
• PKD Foundation: What is polycystic kidney disease?
• Polycystic Kidney Disease Charity