Invitae Polycystic Kidney Disease Panel


Test description

The Invitae Polycystic Kidney Disease Panel evaluates PKD2 and PKHD1, which are two genes that are known to be associated with polycystic kidney disease (PKD). PKD2 is associated with autosomal dominant polycystic kidney disease (ADPKD) and PKHD1 is associated with autosomal recessive polycystic kidney disease (ARPKD).

For at-risk individuals and individuals with clinical features consistent with PKD, identifying a pathogenic variant in one of these two genes early increases the chances of successful treatment of the liver, renal, vascular, and pulmonary manifestations that are associated with ADPKD and ARPKD. Genetic testing can help determine what surveillance and treatments are appropriate, provide a patient information on which agents to avoid, and guide lifestyle-modification, family-planning, and intervention recommendations. It may also increase the amount of time that a patient has to select unaffected family member for donor transplantation.

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Primary panel (2 genes)


Alternative tests to consider

Polycystic kidney disease is a member of a class of disorders called ciliopathies. Ciliopathies are caused by pathogenic variants in genes that affect the function of cilia—the hair-like structures on the surface of cells. Ciliopathies share many overlapping symptoms, often making it difficult to distinguish between them based on clinical presentation alone.

The Invitae Sensory Ciliopathies Panel has been designed to provide a broad genetic analysis of this class of disorders and may be considered as an alternative to testing for a specific disorder. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.

Autosomal dominant polycystic kidney disease (ADPKD)
Autosomal recessive polycystic kidney disease (ARPKD)

Autosomal dominant polycystic kidney disease (ADPKD) is caused by pathogenic variants in the PKD1 and PKD2 genes. It is characterized by the formation of cysts in the kidneys. Cysts can also develop in several organs outside of the kidneys, including the liver, pancreas, seminal vesicles, and arachnoid membranes. Additional clinical features and complications include end stage renal disease, hypertension, vascular abnormalities, cardiac valve malformations (aortic root dilatation and mitral valve prolapse), abdominal wall hernias, and chronic abdominal pain.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by pathogenic variants in the PKHD1 gene. ARPKD is characterized by cyst formation in the kidneys and by liver abnormalities associated with congenital hepatic fibrosis. Symptoms may include enlarged kidneys (nephromegaly), an enlarged liver (hepatomegaly), dilated biliary ducts, and abnormal fetal pulmonary development during pregnancy.

Large population studies of families with ADPKD have pathogenic variants that have been identified in PKD1 or PKD2. Of the individuals with identified pathogenic variants, approximately 85% are have variants in PKD1 and approximately 15% have variants in PKD2. It should be noted that the Invitae Polycystic Kidney Disease panel does not include analysis of the PKD1 gene.

Sequencing the PKHD1 gene identifies pathogenic variants in approximately 77%-79% of individuals who survived the neonatal period.

PKD2 is associated with autosomal dominant polycystic kidney disease.
PKHD1 is associated with autosomal recessive polycystic kidney disease.

ADPKD is highly penetrant, typically begins to manifest in adulthood, and can present with variable symptoms and levels of severity. The majority of individuals with ADPKD will develop end stage kidney failure during their lifetime, requiring dialysis and an eventual kidney transplant. Individuals with pathogenic variants in PKD1 typically experience end stage renal disease by the age of 70, though approximately 50% of individuals with pathogenic variants in PKD2 still have functioning kidneys at 70. Significant intra- and interfamilial variability exists, which is likely due to genetic and environmental modifiers.

ARPKD is a fully penetrant, severe multisystemic disorder whose symptoms often begin to manifest prenatally or in infancy. Morbidity and mortality in infancy is as much as 30% and is a result of pulmonary insufficiency and infections. Infants who survive the neonatal period are at risk to develop end stage renal disease and hepatobiliary disease in the first decade of life.

The prevalence of ADPKD at birth is between 1 in 400 and 1 in 1,000 individuals. ADPKD affects over 12 million people worldwide and is responsible for 10% of end stage renal disease cases.

The prevalence of ARPKD in live births is estimated at 1 in 20,000. The carrier frequency in the general population is 1 in 70 individuals.

Radiology findings are typically used to establish a clinical diagnosis of ARPKD and ADPKD. Genetic testing should be considered to confirm the diagnosis, clarify uncertain radiology results, establish recurrence risk, provide disease prognosis, and to potentially screen living donors for transplantation.

As ADPKD is typically an adult onset disorder. Please consider guidelines and position statements from the American College of Medical Genetics (ACMG), the National Society of Genetic Counselors (NSGC), and the American Academy of Pediatrics (AAP) when testing minors.

  1. Audrézet, MP, et al. Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum. Mutat. 2012; 33(8):1239-50. doi: 10.1002/humu.22103. PMID: 22508176
  2. Bergmann, C, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int. 2005; 67(3):829-48. doi: 10.1111/j.1523-1755.2005.00148.x. PMID: 15698423
  3. Chapman, AB, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015; 88(1):17-27. doi: 10.1038/ki.2015.59. PMID: 25786098
  4. Committee on Bioethics. Ethical and policy issues in genetic testing and screening of children. Pediatrics. 2013; 131(3):620-2. doi: 10.1542/peds.2012-3680. PMID: 23428972
  5. Gunay-Aygun, M, et al. PKHD1 sequence variations in 78 children and adults with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis. Mol. Genet. Metab. 2010; 99(2):160-73. doi: 10.1016/j.ymgme.2009.10.010. PMID: 19914852
  6. Harris, PC, Torres, VE. Polycystic Kidney Disease, Autosomal Dominant. 2002 Jan 10. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301424
  7. Ross, LF, et al. Technical report: Ethical and policy issues in genetic testing and screening of children. Genet. Med. 2013; 15(3):234-45. doi: 10.1038/gim.2012.176. PMID: 23429433
  8. Rossetti, S, et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 2007; 18(7):2143-60. doi: 10.1681/ASN.2006121387. PMID: 17582161
  9. Sweeney, WE, Avner, ED. Polycystic Kidney Disease, Autosomal Recessive. 2001 Jul 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301501
  10. Torres, VE, et al. Autosomal dominant polycystic kidney disease. Lancet. 2007; 369(9569):1287-301. doi: 10.1016/S0140-6736(07)60601-1. PMID: 17434405

No management guidelines are currently published for ADPKD and ARPKD. However, in 2015, the Kidney Disease: Improving Global Outcomes Controversies Conference (KDIGO) published a summary on areas of consensus and controversy surrounding ADPKD management, treatment, and evaluation, with the goal of further developing standards of care:

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
PKD2 NM_000297.3
PKHD1 NM_138694.3