Genetic Counseling for Adults With ADPKD: A Q&A With Dr Neera Dahl
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that causes cysts to grow on the kidneys, which can lead to kidney failure. The National Kidney Foundation reports that APDKD is the most common form of polycystic kidney disease and that affected individuals have a 50% chance of passing the condition onto their children.
A recent study, published in the American Journal of Kidney Diseases, explored preimplantation genetic diagnosis counseling in patients with ADPKD. The lead author of the study, Dr Neera K Dahl, answered a few of our questions.
Neera Kanhouwa Dahl, MD, PhD, is an Associate Professor of Medicine in the Section of Nephrology, Yale School of Medicine in New Haven, Connecticut.
Consultant360: So your article is about preimplantation genetic diagnosis (PGD) counseling in ADPKD. Can you tell us more about the genetic factors associated with ADPKD?
Neera Dahl: ADPKD is caused by a mutation in either the PKD1 and PKD2 gene and is characterized by focal development of fluid-filled cysts within the kidneys. Mutations in PKD1 account for approximately 78% of cases while PKD2 mutations comprise 15% of cases. About 0.3% of cases are attributed to mutations in GANAB. PKD1 mutations are more severe and are associated with an earlier median age of end-stage renal disease (ESRD) onset (58.1 years) than PKD2 mutations (79.7 years). The type of mutation influences the course and severity of disease; truncating PKD1 mutations cause more severe disease than nontruncating PKD1 mutations.
C360: PGD can reduce the risk of passing ADPKD to children. What are the risks and other benefits of PGD?
ND: PGD is performed prior to transferring the embryo into the womb, and thereby eliminates the difficult decision of early term abortions of affected pregnancies diagnosed prenatally. This procedure also allows embryos to be screened for aneuploidy. For couples where pregnancy termination is not an option, PGD with in-vitro fertilization (IVF) may be an ethically preferable option. The offspring of an individual with ADPKD possess a 50% chance of disease inheritance. PGD reduces this risk to 1% to 2%.
Risks of PGD to the mother and fetus include increased risk for multiple gestations, a small increased risk of birth defects, ovarian hyperstimulation syndrome, and ectopic pregnancy, as well as egg-retrieval procedure complications (bleeding, infection, or damage to the bowel, bladder, or blood vessels), stress, and anxiety. It should also be noted that IVF with PGD does not guarantee that pregnancy will be achieved or a normal pregnancy outcome.
C360: What are the clinical features that predict high risk progression to ESRD in patients with ADPKD?
ND: Features that predict high risk progression to ESRD in patients with ADPKD include a large height-adjusted total kidney volume, genotype, early onset of hypertension, and a urologic event (gross hematuria or cyst hemorrhages, cyst infections, or flank pain related to cysts) before age 35 years.
C360: In your opinion, do you think all patients with ADPKD should undergo genetic counseling when planning a family? Why or why not?
ND: Yes, all patients with ADPKD should receive genetic counseling. Ideally genetic counseling should be provided at the time of disease diagnosis, and then later when patients are considering starting families. The extent to which a patient chooses additional counseling regarding assisted reproductive technology or PGD is a personal choice based on patient beliefs, experience, and preferences; and either decision should be supported.
—Amanda Balbi, managing editor, Consultant360
RELATED READING:
Murphy EL, Droher ML, DiMaio MS, Dahl NK. Preimplantation genetic diagnosis counseling in autosomal dominant polycystic kidney disease [published online March 30, 2018]. Am J Kidney Dis. https://doi.org/10.1053/j.ajkd.2018.01.048.