Results: Patient with autosomal dominant polycystic kidney disease

A 29-year-old man has a diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and is under the care of a nephrologist for management of hypertension and to monitor renal function. He has a parent with ADPKD who is on dialysis and awaiting renal transplant, and two adult siblings who are asymptomatic and have not undergone any form of screening. He has two children aged five and two. The patient is requesting information about genomic testing and wishes to know what advice to give to his relatives.

• ADPKD is inherited in an autosomal dominant pattern. This means that each child and sibling of an affected individual has a 50% chance of also having the condition.
• Most individuals with ADPKD have an affected parent; however, about 10% will have no parental family history after screening. This information is important for genetic counselling and most likely represents a de novo case.
• At-risk individuals can be offered screening or predictive genomic testing after appropriate counselling has been offered by someone experienced in managing the condition.
• Screening in children and adults can take the form of assessing blood pressure and kidney function and imaging for renal cysts.
• Predictive genomic testing in children and adults is carried out by clinical genetics services and requires the identification of the familial genetic variant. For this reason, testing is initially carried out on an affected family member.
• Genomic testing in the presenting affected individual can be considered as per the National Genomic Test Directory eligibility criteria. For more information, see Adult with unexpected finding of multiple kidney cysts and Patient with polycystic kidney disease planning a pregnancy.
• Identifying the causal genetic variant will allow at-risk family members to consider predictive genomic testing.
• Targeted genomic testing should be considered for relatives of an individual who has already undergone genomic testing for ADPKD and in whom the familial variant is known.
• R240 Diagnostic testing for known mutation(s) can be offered to clinically affected family members who meet both of the following criteria:
  • the patient is clinically affected with the condition and the familial variant has already been identified in a relative; and
  • the diagnosis has had molecular confirmation (this is required to guide management).
• For asymptomatic, undiagnosed at-risk family members (first-degree relatives), R242 Predictive testing for known familial mutation(s) can be offered (undertaken by clinical genetics services only).

• Refer the affected individual for genetic counselling. A routine referral is usually indicated, but an urgent referral to clinical genetics services should be made if the patient is currently pregnant, and considered if living-related kidney transplantation is being planned.
  • Note that there are regional differences in referral processes for genetic counselling. In addition to clinical genetics services, referral to nurse-led clinics, regional renal-genetic multidisciplinary teams and nephrologist-led clinics may be possible.
• Counsel the affected individual about the chance of their children and/or siblings inheriting the condition.
• Encourage the sharing of this information with at-risk family members, including the results of genomic testing if known. This information is particularly relevant for first-degree relatives, but may also become relevant to members of the wider family if genomic testing identifies those who have inherited the variant.
• Strategies for sharing this information where communication barriers exist (for example, family estrangement) will be discussed with the patient during genetic counselling if required.
• Advise the patient that clinically affected family members, who may have features such as high blood pressure, kidney pain, haematuria and/or frequent urinary tract infections, should discuss with their nephrology clinician a referral for genetic counselling. Genomic testing may be offered if appropriate and if the familial variant is known.
• Advise the patient that at-risk asymptomatic family members, including children, can request a referral for genetic counselling via their GP. Predictive genomic testing may be offered if appropriate and if the familial variant is known. If genomic testing has not identified the familial variant, renal surveillance may be discussed instead.
• Guidelines for screening and genomic testing in children with, or at risk of developing, ADPKD are available, and cases should be discussed with clinical genetics and paediatric nephrology services.
• Inclusion of the following in any genetic counselling or clinical genetics referral will aid assessment of the patient:
  • details of the patient affected by ADPKD (for example, full name, date of birth and address);
  • whether any relatives have been seen by clinical genetics and, if so, in which service;
  • information about the familial genetic variant (if known); and
  • whether the patient is currently pregnant (an urgent referral would be required).
• Signpost the patient and family to sources of support and further information (see the resources section below).
• 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

• GeneReviews: Polycystic kidney disease, autosomal dominant
• KDIGO: Autosomal dominant polycystic kidney disease (ADPKD)
• MedlinePlus: Polycystic kidney disease
• NHS England: National Genomic Test Directory
• NHS Genomic Medicine Service: Signed Off Panels Resource
• Orphanet

References:

• Dudley J, Winyard P, Marlais M and others. ‘Clinical practice guideline monitoring children and young people with, or at risk of developing autosomal dominant polycystic kidney disease (ADPKD)‘. BMC Nephrology 2019: volume 20, article number 148. DOI: 10.1186/s12882-019-1285-2

For patients

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