PGD

Preimplantation Genetic Diagnosis (PGD) for Autosomal Recessive Polycystic Kidney Disease (ARPKD)

It is now possible for physicians to offer preimplantation genetic diagnosis (PGD) for autosomal recessive polycystic kidney disease (ARPKD) to couples at risk of bearing a child with this disorder. The PGD procedure allows genetic testing to be performed on early embryos before implantation for the purpose of selecting only those embryos that are unaffected by ARPKD for uterine transfer.

Children’s Hospital of Wisconsin, Froedtert Hospital and the Medical College of Wisconsin offer PGD for ARPKD.

Autosomal polycystic kidney disease (ARPKD) and PGD

ARPKD is a rare genetic disorder that affects 1 in 10,000 persons in the general population. It is a chronic and progressive disease that causes eventual kidney failure and liver abnormalities. The onset of symptoms is generally from birth to adolescence; rare patients present later with predominantly hepatic presentations. Approximately 50% are diagnosed prenatally. There is no cure for ARPKD. Early newborn death occurs up to 30% of the time most often from pulmonary hypoplasia (underdeveloped lungs) caused by oligohydramnios (decreased amount of amniotic fluid), not from kidney failure. Ventilator support may help the infant survive the newborn period after which the chances of long-term survival improve substantially.

ARPKD is an autosomal recessive genetic disorder. Abnormalities of a single gene, Polycystic Kidney and Hepatic Disease 1 (PKHD1), are the cause of 99% of all ARPKD. In most cases both parents are carriers of the abnormal gene, having one normal gene and one abnormal gene. The carrier frequency for this gene is 1 in 50. These individuals are asymptomatic. When both parents pass the abnormal gene to a pregnancy the child is then affected. Typically there is no prior family history of the disease and the parents usually do not know that they are carriers for the abnormal gene. A DNA test can detect ARPKD. The DNA test uses polymerase chain reaction (PCR), a process that takes a small amount of DNA and makes many copies of it. This copied DNA can be tested to determine whether the PKHD1 genes are normal or abnormal.

Couples who are known to be carriers and/or have had a child with ARPKD and who are considering a pregnancy face a 1 in 4 (25%) chance in each future pregnancy of having a child with the disease. Some couples opt for prenatal diagnosis during pregnancy to determine whether a pregnancy is affected.

An alternative to prenatal testing for ARPKD is now available using in-vitro fertilization (IVF) with PGD to identify an unaffected embryo. In-vitro fertilization (IVF) is the process of combining eggs and sperm to form embryos in the laboratory. IVF is often used to help couples with infertility have a child. Preimplantation genetic diagnosis (PGD) is a procedure to analyze the genetic make-up of embryos formed through IVF for determination of disease status. Couples at risk for ARPKD can use PGD to test for this disease. Based on this analysis, embryos that are not affected with ARPKD can be selected for transfer to the uterus to establish a pregnancy.

PGD process for the purpose of ARPKD testing

Parents and their affected child, if/when possible, will first undergo blood tests to determine whether the PGD process will be feasible. If these tests show that PGD is possible, the parents will undergo an IVF cycle to form embryos.

The embryos created are sampled on the third day of development when they have approximately 6 to 8 cells. One or two cells are taken from each embryo for testing using PCR. The embryo is incubated until testing is complete. Each embryo has a 1 in 4 chance of being affected with ARPKD. By testing these cells for deletions in the PKHD1 gene, only those embryos determined to be unaffected (having one or two working copies of the gene) are selected for transfer back into a woman’s uterus. Thus, the chance to have an unaffected pregnancy is greatly increased.

The Risks of PGD

The biopsy technique required to perform PGD has been in use since 1990. The likelihood of damage to an embryo during the removal of cells is low, but it can occur. This can result in a decreased chance of embryo survival. When compared to IVF without PGD, there is a somewhat decreased chance for embryo survival among embryos that have undergone PGD. IVF with PGD is not known to lead to an increased chance for congenital abnormalities, birth defects, mental retardation, or other abnormal development when compared to natural pregnancies. However, a normal pregnancy outcome is not guaranteed.

Overall, PGD is an accurate process for determining whether an embryo is affected with ARPKD. There is a small risk of error or technical limitation that will prevent us from determining whether the sampled embryos have ARPKD. Because of this and the fact that we do not test for other genetic conditions or chromosome problems, the option of testing early in pregnancy through prenatal diagnosis is available.

Preventative Measure during PGD Cycle

It is important for couples undergoing PGD to alter their sexual activity during the PGD cycle. Couples must refrain from intercourse until the cycle is complete.

Cost of PGDM

IVF with PGD is expensive. Insurance companies generally do not cover the cost of IVF with or without PGD. We will provide you with a detailed cost analysis for IVF and PGD at your request.

Contact Information

Requests for information regarding the Children’s Hospital of Wisconsin, Froedtert Hospital and Medical College of Wisconsin PGD program and IVF can be obtained by contacting the Reproductive Medicine Clinic at (414) 805-7370 or by using our Contact Us form. Information regarding PGD for the purpose of ARPKD testing can be discussed in more detail with our geneticist or genetic counselor.

Date: Jan. 22, 2009

Last Review Date: July 21, 2009

Online Editor(s): Richard Petre