Presentation: Patient with polycystic kidney disease planning a pregnancy

A young couple are planning their first pregnancy. The woman has recently been diagnosed with autosomal dominant polycystic kidney disease (ADPKD) following a screening ultrasound scan that was performed because her own mother is affected and has recently had a living related kidney transplant. The couple are concerned about the risk to their future child.

You should think about genomic testing:

• to confirm the diagnosis of ADPKD if required for management purposes; and/or
• if, after genomic counselling, a couple are planning either preimplantation genetic testing or invasive prenatal diagnosis.

• Collect a detailed family and personal health history from the couple.
• Ensure that the affected individual is referred for expert nephrology and obstetric review, including medication review, prior to conceiving if complications such as hypertension, chronic kidney disease or a family history of intracranial aneurysm are present.
• Refer to clinical genetics for review and discussion about reproductive options including preimplantation genetic testing for monogenic disease (PGT-M).
• 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 test is most suitable. The appropriate tests for ADPKD are:
  • R193 Cystic Kidney Disease: This indication is used to investigate single gene causes of kidney cysts. This test is carried out by whole genome sequencing (WGS).
  • R240 Diagnostic testing for known variant(s): This indication should be used if a disease-causing variant has been identified in another family member.
• For tests that are undertaken using WGS, including R193, 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:
  •  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 clinicians

• DynaMed (clinical decision support and shared decision-making tools): Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• GeneReviews: Polycystic Kidney Disease, Autosomal Dominant
• 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)
• National Institute for Health and Care Excellence (NICE): Tolvaptan for treating autosomal dominant polycystic kidney disease
• NHS England: National Genomic Test Directory
• UK Kidney Association Annual Report 2021
• UpToDate (clinical decision support resource): Autosomal dominant polycystic kidney disease (ADPKD): Treatment

For patients

• PKD Charity