Our DNA Day Miracle

Part 2 of a special DNA Day post. If you have not already done so, I suggest that you first read Part 1: Autosomal Dominant Inheritance: Brugada Syndrome


How young should individuals be DNA tested? At 18? Younger? You may recall I discussed Newborn Screening in a post a week ago. How about testing when they get to the 8 cell level? That is typically at Day 3 after the egg is fertilized. This is not science fiction. This is happening now. 

We have bad family planning. Between my wife and I we have 8 biological (plus 2 non-biological) grandsons and NO granddaughters. It almost wasn't like this. For a while we thought we had a legitimate shot at having a granddaughter this time. More about that later.


Brugada in our extended family

You will recall in part one of this post that Brugada, as an autosomal dominant disorder, has a 50% probability of being inherited by any child of an affected individual. In a family with 4 children there is a 1 in 16 chance that the disorder will be inherited by all 4. That is apparently what happened in the family of one of our daughters-in-law. 

The first devastating diagnosis was made when her older brother was in his late thirties. He subsequently had a defibrillator surgically implanted. Soon thereafter my daughter-in-law was confirmed to have the symptom and received a defibrillator as well. Her oldest son was turning 2. At the time the youngest child to have a surgically implanted defibrillator was thought to be 4 1/2. In that case this risky process was performed because he had a younger sibling experience sudden death from such a disorder. My grandson was tested and to all our great relief he had not inherited the autosomal dominant gene. 

When my second grandson was born, my job was to meet my son at the curb outside the hospital and take a blood sample gathered in the delivery room and FedEx it overnight to a lab for testing. Only after this process was underway was I allowed to go inside the hospital and welcome my new grandson. Once again the Brugada bullet had been dodged.

By then we were learning more about Brugada. More comprehensive family testing was conducted. That disclosed the parent who carried the gene and some extended family members who did not. My daughter-in-law's youngest brother was also diagnosed and subsequently had a defibrillator installed.  

With 20/20 hindsight it is suspected that the other sibling of this family also inherited this disorder. He died in 1980 of what was then though to be sudden infant death syndrome (SIDS) at age 2 months. But then we did not know about Brugada. 

When my son and daughter-in-law decided they wanted to have a third child they turned to DNA testing to sidestep any additional Brugada bullets.


Preimplantation Genetic Diagnosis (PGD): the theory


Penn Medicine, The University of Pennsylvania website describes the process of DNA testing at the 8 cell level:

Preimplantation genetic diagnosis (PGD) is a screening test used to determine if genetic or chromosomal disorders are present in embryos produced through in vitro fertilization (IVF). Preimplantation genetic diagnosis screens embryos before they are transferred to the uterus so couples can make informed decisions about their next steps in the IVF process. Embryos unaffected by the genetic or chromosomal disorder can be selected for transfer to the uterus.

 Preimplantation genetic diagnosis is available for couples undergoing IVF. The steps of the IVF process include:

·        Medications are used to suppress a woman's natural menstrual cycle.
·        Her ovaries are then stimulated with medications to produce multiple follicles, each of which may contain an oocyte (egg).
·        The eggs are retrieved from the woman's ovary by a needle placed in the vagina.
·        In the lab, the eggs are combined with the male partner's sperm in a special culture medium that allows fertilization and the growth of high–quality embryos.
Embryo biopsy may be performed after 3 days of culture in the laboratory. The embryos are typically 8-cell embryos on Day-3 and the process involves the removal of one to two cells.After the biopsy and following receipt of the results from the genetic/chromosomal testing, embryo(s) of the best quality that are not affected by the genetic disorder or chromosomal abnormality) are selected for transfer to the uterus. 

The results of preimplantation genetic diagnosis are reported to the couple no later than the morning of their scheduled day for embryo transfer. Typically this is five days after oocyte retrieval and in vitro fertilization are performed. Of the embryo(s) that are not affected by the genetic disorder or chromosomal abnormality, the best quality embryo(s) are selected for transfer to the uterus. If additional unaffected and good–quality embryos are available, they may be cryopreserved for a future embryo transfer.

Preimplantation genetic diagnosis provides diagnostic information based on the analysis of a single cell. Therefore, prenatal testing is still recommended and currently remains the standard of care.

How much does this cost?

One of my stepsons asked my son, "Isn't this process incredibly expensive?" 
My son replied that he had already done a cost-benefit analysis and that the process would cost about half what it would cost to care for a child that carried the Brugada gene.

According to WebMD:

The average cost of an IVF cycle in the U.S. is $12,400, according to the American Society of Reproductive Medicine. This price will vary depending on where you live, the amount of medications you're required to take, the number of IVF cycles you undergo, and the amount your insurance company will pay toward the procedure. 

The cost of an IVF cycle with preimplantation genetic diagnosis is higher.


PGD in practice

My daughter-in-law went through a series of shots to stimulate her ovaries. The result was the production of 28 fertilized eggs. On Day 3 these had reached the 8 cell level of development and were tested. In this case the predicted 50% rate of affected eggs from autosomal dominant inheritance was exactly on target. 14 of the fertilized eggs carried the Brugada gene. Of the 14 that did not, all but 2 were immature or had other abnormalities that did not make them likely to produce a healthy baby. The two that looked the most healthy were both girls.

One of the healthy embryos was implanted. Our daughter-in-law, who is a surgical gynecologist, cautioned us not to get our hopes up because there was only a 35% chance a pregnancy would result. She was prescient. No pregnancy developed so subsequently the second embryo was implanted. Again no pregnancy resulted.

After a decent interval the entire process was repeated. From this cycle only one viable embryo resulted. He was a boy. HE DID RESULT IN A PREGNANCY. And ironically and most appropriately he was born today on DNA Day at Vanderbilt University Hospital here in Nashville! 

My new grandson is not the first child to avoid potential genetic disaster by this type of testing. The first of which I am aware was reported by Oxford University in July, 2013.

A first baby has been born to a couple in the USA going through IVF and involving the use of a new embryo screening approach. The method uses the latest DNA sequencing techniques and aims to increase IVF success rates while being more affordable for couples.

The two babies reported by Oxford University resulted from embryos that were screened at the 5 Day stage.

My grandson was not even the first to be born with the assistance of genetic screening in my daughter-in-law's family. Her brother, the first family member to get a Brugada diagnosis, became a first time father in November after using PGD in the NYC area. However, the young man you see pictured with me is the first of MY grandchildren to benefit from PGD and may have been the first to be born to a woman with a surgically implanted defibrillator -- the fate we are hoping to avoid for her son.