Presentation: Fetus with cystic renal disease

A woman presents for her fetal anomaly screening scan. The scan identifies multiple cysts in both kidneys. No other anomalies are seen.

• Genomic testing should be considered in cases of cystic renal disease, especially when it is bilateral and/or associated with other anomalies.
• Identifying a genetic cause can help with prenatal decision-making and postnatal management, and can provide information about the chance of recurrence in future pregnancies.
• Prenatal testing and diagnosis can be offered in the first trimester for families in which there is a known genetic cause.

• 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.
• 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 being considered (see below).
• The fetal medicine team will decide which test 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. This is likely to include the below.
  • R22 Fetus with a likely chromosomal abnormality. This will process both:
    • • R22.1 Genome-wide common aneuploidy testing; and
      • R22.2 Chromosomal microarray.
  • Large echogenic kidneys with a normal bladder is an indication for fetal exome sequencing, even if no other systems are affected:
    • 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 (RoD) form.
  • Where a specific genetic condition is considered likely or there is a relevant family history, further guided genomic testing may be recommended.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (RoD) form.
• Parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
• For R21 Fetal anomalies with a likely genetic cause, you will need to:
  • ensure that the required multidisciplinary discussions have taken place, including fetal medicine, clinical genetics and the regional specialist R21 laboratory, and that there is an agreement that R21 can be offered;
  • inform your local laboratory of the plan for R21 testing, so that they can arrange the necessary exports to the specialist R21 laboratories in a timely fashion;
  • fill in the R21-specific test order form;
  • take informed consent for both parents, documented on R21-specific RoD forms;
  • send blood samples for both parents to the local laboratory (if only one parent is available, let the lab know – testing can still proceed, but there will be a small reduction in diagnostic yield); and
  • arrange and send a chorionic villus sample or amniocentesis sample for the fetus.
• Note that, in Scotland, referral to clinical genetics is required for consideration of rapid prenatal exome testing.
• All of the above tests are DNA based and require an amniocentesis or chorionic villus sample, or a fetal blood sample in an EDTA (typically purple-topped) tube. For more information about different sample types, 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

• The Fetal Medicine Foundation: Autosomal dominant polycystic kidneys
• The Fetal Medicine Foundation: Autosomal recessive polycystic kidneys
• The Fetal Medicine Foundation: Multicystic kidneys
• NHS England: National Genomic Test Directory
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: National Genomic Test Directory Clinical Indication R21 Rapid prenatal exome sequencing test request (PDF, two pages)
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Record of discussion regarding prenatal exome sequencing (PDF, two pages)
• Sands: Consensus guidelines on the communication of unexpected news via ultrasound

For patients

• InfoKID: Multicystic dysplastic kidney (MCDK) information
• Massachusetts General Hospital for Children: Fetal multicystic dysplastic kidney (MCDK): What you need to know
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Information on prenatal exome sequencing for parents (PDF, two pages)