Why Us? Understanding Preimplantation Genetic Diagnosis

By Dr. Mark D. Johnson

Why us? he asked in frustration. I could see her eyes welling up with tears. It was a question that this couple had asked themselves many times over the past few years since their 3-year daughter was first diagnosed with a genetic neurodegenerative disease, infantile metachromatic

leukodystrophy (MLD).

Why were we both chosen to be carriers of MLD out of all of the millions of people in the world? asked Christine, exhausted, as tears slowly filled her eyes. She was almost too emotional to speak. Her husband added, What are the odds Doc, of my wife and I meeting and having a daughter born with a rare disease that we’ve never heard of, and that no one in our families has ever had? John showed me a photo on his phone; Here we are Doc, that’s Cassidy when she was a baby.

I saw the heartbreaking sadness in Christine and John’s eyes and the fatigue on their faces. They told me about Cassidy, their only daughter, who was afflicted with MLD. Cassidy never learned to walk and, sadly, now at 3 years old, required 24-hour a day parental nursing care. She was bedridden, blind and couldn’t speak words. Her development had deteriorated to that of an infant.  She was not expected to live past the next year.

We are here to see if you can help us have a healthy son or daughter. We love our Cassidy, but we don’t want to risk bringing another child into this world with MLD.”

After Cassidy’s diagnosis was determined, Christine and John had met with a genetic counselor and through genetic counseling they understood the odds of having another child with MLD.  They knew that each child they conceived would have a 25% chance of being affected with MLD.

Here are some of the statistics behind genetic diseases like MLD:
MLD is a recessive genetic disease, which means that a person can have an abnormal mutation in one of their two genes that reduces the gene’s function. The remaining normal gene of the pair functions normally and produces enough protein to prevent carriers of the disease gene, such as Christine and John, from being affected with the disease. However, when carriers for recessive diseases reproduce, each carrier has a 50% chance of transmitting his or her abnormal mutant gene into their sperm or egg. This results in a 25% chance of having a child that carries the abnormal mutation in each of their two genes (.5 x .5 = 25% chance). When each of the two genes has an abnormal mutation that prevents the gene from functioning, then a deficiency in the gene’s product results in the child’s cells, and the child is affected with the disease, in this case, metachromatic leukodystrophy (MLD).

A genetic counselor taught Christine and John about the genetics of MLD, their reproductive risks as a couple, and their reproductive options. The option that offered the most hope for Christine and John was preimplantation genetic diagnosis (PGD). Preimplantation genetic diagnosis is the screening and detection of genetic diseases or chromosome abnormalities in eggs or embryos prior to conceiving an intrauterine pregnancy.

I also explained preimplantation genetic diagnosis (PGD) to Christine and John. The advantage of PGD is that couples at increased risk for producing children with incurable genetic diseases, such as Christine and John, are provided the opportunity to have healthy children.

The PGD process involves the following steps that take place with in vitro fertilization (IVF):
1. In the IVF lab, one or two cells are removed from the early embryos as they develop.
2. These cells undergo genetic analysis to determine which of the embryos are normal and not affected with the specific genetic disease under study.
3. After two days, PGD test results are available. The embryos that are not affected with the genetic disease are transferred into the uterus to establish a pregnancy.

I explained to Christine and John that each of the embryos they conceived through the IVF process would have a 75% chance of not being affected with MLD and would therefore be eligible for transfer into the uterus to produce a pregnancy.  More specifically, each of Christine and John’s embryos would have a 25% chance of being genetically normal and not having the mutation in their two normal genes, and each of their embryos would have a 50% chance of being unaffected carriers, such as Christine and John, with one normal gene and one mutation gene.

I further explained to Christine and John that each of the embryos they conceived through the IVF process would have a 25% chance of being affected with MLD, and would therefore not be a candidate to produce a pregnancy.

Our hope was that by conceiving their embryos through IVF and screening their embryos for MLD through PGD genetic testing prior to implantation in the uterus, that Christine and John would have a healthy child not affected with MLD.

Our hopes and prayers were answered. Today, after going through the process of IVF and PGD, Christine and John are the proud parents of healthy 5-year old twin sons who are not affected with MLD.

In my next blog post, I will explain why I recommend that my patients consider having genetic carrier screening for certain genetic diseases, even when they don’t have a family history of any known genetic diseases.

Mark D. Johnson, M.D., FACOG, FACMG has practiced reproductive medicine and fertility in the Phoenix valley since 2000. He came to Phoenix with extensive professional experience in reproductive medicine. His background is unique in that he is both an experienced reproductive endocrinologist and infertility specialist and a clinical geneticist. He is Board Certified in Obstetrics and Gynecology with subspecialty Certification in Reproductive Endocrinology-Infertility and is Board Certified in the specialty of Medical Genetics. To make a consultation with Dr. Johnson at Arizona Reproductive Medicine Specialists, call (602) 281- 9032.