Presentation: Child with an ectopic kidney

A 6-year-old boy was found to have an ectopic right kidney located in the pelvis on an ultrasound scan for unexplained abdominal pain. The left kidney was normal in size and location. His renal function was normal. His 36-year-old mother had been referred to the renal clinic last year after being identified with chronic kidney disease in pregnancy. Her renal ultrasound showed unilateral renal agenesis.

Consider genomic testing for:

• clinically significant non-syndromic congenital anomalies of the kidney and urinary tract (CAKUT), if the patient also has a first-degree relative with CAKUT or unexplained end-stage renal disease;
  • in some cases, additional family history information may suggest that testing would be beneficial – you can check criteria with your local testing laboratory;
• when CAKUT occurs with additional syndromic features, as it is likely to have a monogenic cause in these instances; and/or
• CAKUT with a personal or family history of diabetes or renal cysts.

Families in which there are only the minor forms of CAKUT are unlikely to benefit from genomic testing, for example: isolated vesico-ureteric reflux, duplex kidney, posterior urethral valves.

• 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 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 panels best suits the needs of your patient/family:
  • R199 Congenital anomalies of the kidney and urinary tract – familial: This indication uses genome-wide microarray to identify any copy number variants that might be associated with CAKUT.
  • R27 Paediatric disorders and R89 Ultra-rare and atypical monogenic disorders: These tests may be considered for individuals with complex or syndromic presentations. R89 includes microarray and whole genome sequencing (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.
  • R141 Monogenic diabetes: This test should be used when there is a personal or family history of diabetes or renal cysts. It includes whole exome sequencing or a medium-sized panel and multiplex ligation-dependent probe amplification (MLPA).
  • R240 Diagnostic testing for known variants(s): This indication can be used if a patient who is clinically affected with CAKUT has a family member with a known pathogenic or likely pathogenic variant. (Note that variable penetrance is common.) In this situation, the laboratory will only test for the known familial variant.
  • R242 Predictive testing for known familial variants(s): This indication is for a predictive (also known as presymptomatic) test and should be used for unaffected individuals who have a family member with a known pathogenic or likely pathogenic variant. This test can only be requested by clinical genetics.
• For tests that do not include WGS, including R199, R141, R240 and R242:
  • you can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms.
• For tests that are undertaken using WGS, including R27 and R89, 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 in completing WGS-specific forms).
• 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.

For clinicians

• Genomics England: NHS Genomic Medicine Service (GMS) signed off panels resource
• MedlinePlus: Congenital anomalies of kidney and urinary tract
• NHS England: National Genomic Test Directory
• UK Kidney Association: Congenital Anomalies of the Kidneys and Urinary Tracts, Rare Disease Group

For patients

• infoKID (information for parents and carers of children with kidney conditions)
• UK Kidney Association: Congenital Anomalies of the Kidneys and Urinary Tracts