Presentation: Fetus with cystic renal disease

A woman presents for her fetal anomaly screening scan. The scan identified multiple cysts in the baby’s right kidney. The left kidney appeared normal with no anomalies seen.

• Genomic testing should be considered in cases of cystic renal disease, especially when it is bilateral and/or associated with other anomalies, in order to estimate the chance of recurrence.
• Prenatal testing and diagnosis can be offered in the first-trimester for families where there is a known genetic cause.

• Consult the National Genomic Test Directory. From this directory 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 those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Explore the woman’s pregnancy, medical and family history.
• Refer to local guidance regarding fetal medicine referral (a further review in a fetal medicine unit is usually warranted).
• The fetal medicine review will determine whether genomic testing is appropriate, and referral to clinical genetics will be considered. Referral to clinical genetics is not routinely indicated unless fetal exome sequencing is planned (see below).
• The fetal medicine team will decide which testing is most suitable for the patient and/or discuss the case with a multidisciplinary team, depending on the specific clinical scenario and the patient’s wishes.
• Depending on the clinical scenario, a range of different genomic tests may be considered:
  • Where there is an isolated abnormality:
    • R22 Fetus with a likely chromosomal abnormality. This will process both:
      • R22.1 Genome-wide common aneuploidy testing; and
      • R22.2 Chromosomal microarray.
  • For certain significant or complex anomalies and/or where above testing is non-diagnostic, fetal exome sequencing may be considered:
    • R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing.
      • Referral to clinical genetics and/or multidisciplinary discussion is required.
      • The clinician requesting the test will be required to complete a record of discussion form.
  • Where a specific genetic condition is considered likely or there is a relevant family history, further guided genomic testing my be recommended.
• For tests that are undertaken using whole genome sequencing (WGS), you will need to:
  • complete an NHS GMS test order form with details of the proband and parents. Include details of the phenotype (refer to human phenotype ontology (HPO) terms or the clinical summary) 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. Note that, if you are undertaking trio testing of an affected child and their parents, you will need three of these forms. (see How to complete a record of discussion form for support).
  • parental samples should be submitted alongside the child’s sample. This is called trio testing. If this is not possible, such as when testing a child in care or a parent is unavailable for testing, the child may be tested as a singleton.
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub (GLH).
  • include details of the phenotype in the test order form (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
  • 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.
• For all these tests, an amniocentesis or chorionic villus sample or fetal blood sample (in an EDTA tube) is required.
• For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful.
• 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

• Fetal Medicine Foundation: Autosomal dominant polycystic kidneys
• Fetal Medicine Foundation: Autosomal recessive polycystic kidneys
• Fetal Medicine Foundation: Multicystic kidneys
• NHS England: National Genomic Test Directory and eligibility criteria

References:

• Alt S, Arezina J, Arnold J and others. ‘Consensus guidelines on the communication of unexpected news via ultrasound.’ White Rose Research Online. DOI: 10.5518/100/24

For patients

• InfoKID: Multicystic dysplastic kidney (MCDK) information
• Massachusetts General Hospital: Fetal multicystic dysplastic kidney (MCDK) information