Renal Cysts and Diabetes (RCAD)

The Renal Cysts And Diabetes (RCAD) syndrome is caused by heterozygous variants in the HNF1B gene (Bingham et al. 2000 Kidney Int 57:898-907; Edghill et al. 2006 J Med Genet 43:84-90). Whole gene deletions account for up to 50% of variants, and 40% of HNF1B variantsare de novo. An absence of family history of renal disease or diabetes should therefore not exclude genetic testing for RCAD.

Clinical presentations of RCAD usually include at least two of the following:

• Unexplained renal cystic disease (renal cysts may be detected in utero)
• Renal dysplasia
• Renal hypoplasia/agenesis
• Early onset non-insulin dependent diabetes
• Reproductive tract malformations
• Hyperuricaemia and early onset gout
• Hypomagnesaemia
• Deranged liver function

Neurodevelopmental disorders such as autism are observed in approximately 40% of patients with an HNF1B whole gene deletion occurring as part of a chromosome 17q12 microdeletion, but are not associated with HNF1B intragenic mutations (Clissold et al. 2016 Kidney Int 90: 203-211).

The severity of the renal phenotype is variable, from enlarged cystic kidneys incompatible with life to normal renal development and function, and HNF1B variants are a rare cause of diabetes in the absence of known renal disease (Edghill et al. 2013 Diabet Med 30:114-117).

Further information is available at diabetesgenes and rarerenal about RCAD and HNF1B variants.

Analysis of the HNF1B gene in renal cysts and diabetes (RCAD).

Visit the NHS Genomic Test Directory 

Eligibility criteria for genomic tests can be found in the National Genomic Test Directory.

This lists the clinical specialties that would be expected to request for a given clinical indication and sets out which patients should be considered for testing.

All samples for genomic testing should be accompanied by a fully completed request form.

The request form should include as much clinical information about the patient or family member, family relationships and the requested test code (R number). All request forms must indicate either a specific disorder/gene(s) to be investigated or, a request to extract and store DNA.

This form should be used for the majority of test requests.

Please do not download and store this on your desktop or system. The form is regularly updated. Our recommendation is to save or bookmark a link to our website to ensure you are working with the most up-do-date version.

Download the latest version here: GMS Test Order Form v2.3

An appropriate discussion of genomic testing and the possible implications for a patient and their family members must take place before testing is requested.

It is the referring clinician’s responsibility to ensure that the patient/carer knows the purpose of the test and that the sample may be stored for future diagnostic testing. In submitting a sample with a request form, the clinician confirms that informed consent has been obtained for (a) testing and storage (indefinitely) (b) the use of this sample and the information generated from it to be shared with members of the donor’s family and their health professionals (if appropriate). The patient should be advised that the samples may be used anonymously for quality assurance and training purposes.

If stated as a requirement for a specific test, a record of this discussion must be retained within the patient record when a genomic test is ordered.

For more information please view the Consent and Confidentiality in Genomic Medicine guidelines from the Joint Committee on Medical Genetics.

Before sending samples for genomic testing, please ensure you follow the correct preparation and transport guidelines. This includes information on sample types, volumes, handling, labelling, and packaging standards.

For a full list of sample requirements and transport guidance, please visit the samples and transport page of the website. 

Turnaround times (TATs) for genomic tests are continually refined through ongoing reviews of testing standards.

Results will be returned to the email account or clinician listed on the request form.

Visit the results and turnaround page for more information.

Visit the results and turnaround page for more information.