The results are in and the marathon continues! We were waiting in anticipation for the results from Athena Diagnostics. In addition to testing for the two main causes of congenital nephrosis, mutations of the NPHS1 and NPHS2 gene, the lab also tested two of the rarer causes of baby kidney disease, mutations of the WT1 and LAMB2 genes. Unfortunately, the lab was not able to provide any definitive answers. We know for sure that Boston does not have congenital nephrosis of the Finnish type, because there were no mutations of the NPHS1 or NPHS2 genes. However, there were issues with the other two genes that make the doctors think it is likely that Boston will be born with a fatal syndrome that can also cause congenital nephrosis. We will not know for sure if he has these syndromes until he is born, but there are markers we will be watching for along the way that will tell us if it is more/less likely. We view this as an opportunity for increased prayer and faith in God’s unending grace and mercy, not to mention his unlimited power to heal both body and soul.
Our doctors received the lab results on September 30, 2008, and spent 24 hours researching and making phone calls to make sure that they had all the available information they could get. We are grateful for their diligence and hard work and are confident in both their knowledge and dedication to finding the correct diagnosis for Boston. Only two labs in the world test the LAMB2 gene, our lab, Athena Diagnostics, and a lab in Germany. The WT1 and LAMB2 genes were so recently linked with congenital nephrosis that Athena Diagnostics just started testing for them in July 2008. Boston is the first prenatal screen of the LAMB2 gene that has been performed; all other screens for the gene were done after the baby was born and the external indicators pointed in the direction of the disease and the genetic screen was done to confirm the syndrome. In our case, we are trying to diagnose the disease based on the gene alone, and will not have the external confirmations until Boston is born.
Our doctors were frustrated by the non-decisive results, but did their best to explain the outcomes and options. There are no additional tests that can be performed to give us more definitive results. Our answers will come after Boston is born. Until then, we wait, prepare, and pray.
We will do our best to try and explain the test results and what the doctors communicated to us. As we have stated previously, the first red flag was the incredibly high AFP result that came with the amniocentesis and the “bright” kidneys on the sonogram. All of the typical diagnoses for a high AFP were eliminated. Two explanations remained: testing Boston’s genes for some known causes of CNS and testing and testing Sarah for some sort of cancer/disease. Sarah has been all but ruled out as a cause for the high AFP.
We were expecting the results to focus around the NPHS1 and NPHS2 genes, because these are the most common. Instead, our results concerned the WT1 gene and the LAMB2 gene, which are the rare, newly discovered genes. The results from the tests of these two genes is where the uncertainty lies.
For each of Boston’s genes, he has two strands, one from Sarah and one from Brian. Understanding these tests requires knowledge of genetics from the freshman year of biology. Each trait, whether it is brown hair, blue eyes, or Pierson Syndrome, is either dominant or recessive. With a dominant trait, you only need the gene from one parent in order to have that trait. With a recessive trait, you would need a gene from both parents in order to have that trait. WT1 is a dominant trait, meaning that only one of the genes that Boston received would have to be mutated. LAMB2 is a recessive trait, meaning that both of the genes Boston received would have to be mutated. In looking at the genes, the lab technicians lay the two strands, one from Sarah and one from Brian, on top of each other and look for changes (variants) or mistakes (mutations).
The WT1 gene came back with what the doctors’ describe as a “variant.” This means that there is a change in the way one of Boston’s WT1 gene reads, but the doctors do not think it is enough to change the way the body performs. The example that our genetic counselor used was to look at the genes like a recipe. If the recipe calls for “sugar,” a mutation would change the word “sugar” to “salt.” This would mess up the whole batch of cookies. A variant is changing the word “sugar” to “suggar.” An experienced cook would look at the word “suggar” and know to add “sugar.” An inexperience cook might not know what “suggar” means and they may leave it out or just quit cooking. What we don’t know is what type of cook Boston is and whether his body will know what to do with the variant. Because mutations of the WT1 gene are dominant, it would only take one mutation for Boston to have this disease; however, so far the change has been classified as a “variant” and not a “mutation.” Athena Diagnostics’ response is that the variant is of “unknown significance.” Our educated guess is that Boston’s body will handle the variant just fine. There are some markers for a mutation of the WT1 gene that we can watch for on the sonogram and so far none of those are present. WT1 gene was so named after “Wilms Tumor,” which is a large tumor that grows on the kidneys when this mutation exists. So far, the sonogram shows that Boston’s kidneys are tumor-free. Another feature would be pseudohermaphroditic genetalia, meaning that we wouldn’t really be able to tell if Boston was a boy or a girl by looking at him from the outside. He is developing into a normal-looking boy, which is another reason we don’t think that the variant of the WT1 gene will cause any syndrome or disease.
Our prayers are going to be focused on the results of the LAMB2 gene. Mutations of the LAMB2 gene are known to cause a disease called Pierson Syndrome. Pierson Syndrome is a recessive disease, so both the gene from Sarah and the gene from Brian would have to be damaged in order for Boston to have Pierson Syndrome. The results from Athena Diagnostics told us that one of the genes is damaged. It was more than just a variant, it was a definite change in the gene and was classified as a mutation. If we knew definitely that only one of the genes was damaged, we would rest a little bit easier, because that would mean that Boston would be a carrier for Pierson Syndrome, but he would not have it. The doctors have told us that they cannot guarantee that the other gene is fine; all they can say is that they only found one mutation. It is possible that the other gene is mutated but they didn’t find it. Our prayers are focused squarely on this hope: that Boston has one broken gene and one normal gene and that he will be born without Pierson Syndrome.
Athena Diagnostics’ conclusions about this were as follows: Boston is at least a carrier for diseases related to mutations of the LAMB2 gene. The fact that one mutation was found “increases the likelihood that [Boston] may be affected with [baby kidney disease], even though the second mutation was not identified. However, the result is not definitive for the diagnosis of [baby kidney disease] since known or predicted disease-associated mutations in both alleles were not detected.”
Because of Boston’s high AFP, his “bright” kidneys, and the fact that he has one broken gene, we are preparing for the likelihood that Boston will be diagnosed with Pierson Syndrome after he is born. However, while we are preparing for that possibility, our prayers and hopes will be focused on Boston being born healthy and without complications.
If Boston does have two broken genes, it is likely that he will have Pierson Syndrome. Pierson Syndrome is extremely rare and new on the scene. The first diagnosed case in the US was in 2006. Only 30 cases have been identified in the literature so far worldwide. As we mentioned, Pierson Syndrome is caused by a mutation of the LAMB2 gene. The LAMB2 gene is so named because it produces the B2 chain of the laminin protein. There are twelve genes that help make the laminin protein: LAMA1-LAMA5: LAMB1-LAMB4; and LAMC1-LAMC3. Laminin is critical in forming the structural scaffolding of all of our organs, known as “basement membranes.” A mutation of the LAMB2 gene causes defects in the “glomeular basement membrane” of the kidney. Malfunctions of the GBM can lead to congenital nephrosis, which is discussed in detail below. A mutation of the LAMB2 gene also causes defects in the basement membrane of the eye. Babies born with Pierson Syndrome often have “pinpoint pupils,” called microcoria, due to a weakening of the muscles that dilate the pupils. Some kids are blind because of the changes in the eyes. The mutation of the LAMB2 can also cause a weakening in overall muscle strength (hypotonia) and a slowness of the brain’s reactions (psychomotor retardation).
As is evident from the above description, Pierson Syndrome is very, very bad. Of the 30 cases reported so far, none of the children have survived beyond age 5, usually due to complications with the nephrosis. This was devastating news to us when we heard it. We have taken time to adjust to the idea that we could lose Boston at a very young age.
However, we are encouraged by the fact that so few cases of Pierson Syndrome have been reported. We have recently been provided with studies that outline mutations of the LAMB2 gene that do not cause full-blown Pierson’s. These children, while they still have congenital nephrosis and some ocular abnormalities, generally have milder cases and therefore a more positive outlook. We are looking for information about Pierson Syndrome and are reading everything that is available about the disease. The “newness” of this mutation discovery puts us at an information disadvantage, but it also gives us hope that Boston could have a chance at survival if he does have the disease.
Nephrotic syndrome can be the side effect of some disease or can be the primary effect of certain syndromes. On its own, nephrosis is just a description of symptoms: lots of protein in the urine (proteinuria or albuminuria), swelling of the body (edema) that can cause high blood pressure (hypertension) and high levels of fat in the blood (hyperlipidemia). The flushing out of the proteins also means that a lot of antibodies are flushed out too, so there is also a higher susceptibility to infection. Nephrotic syndrome that occurs in older children and adults can be treated with steroids and so the prognosis (predicted outcome) is positive.
Congenital nephrosis is a different story. It is extremely rare and the prognosis is poor because it is resistant to steroids and other medications traditionally used to treat nephrosis. Congenital nephrosis will usually progress to end-stage renal disease within childhood (with Pierson Syndrome it is usually in the first year). When end-stage renal disease occurs, the kidneys shut down completely and the child can only survive through the use of dialysis. However, dialysis is not a long term solution and the child must receive a kidney transplant. The main complication is that babies/children have to reach at least 20 pounds before they can undergo a kidney transplant. Once end-stage renal failure occurs, it is very difficult to gain weight. The reason no child has survived beyond age 5 with Pierson Syndrome is because most the babies reach end-stage renal disease in the first few weeks or months of life, before they are 20 pounds. Then they can’t gain any weight and so the chance for a transplant is gone. Children with other forms of congenital nephrosis may not reach end-stage renal disease until they are older and so the option of a transplant is more available.
Bonus news about growth: as many of you know, Clark was breastfeed exclusively when he was a baby. Although he was only 7 pounds 10 ounces when he was born, he reached an unbelievable 20 pounds in a mere 3 months! Most babies do not reach 20 pounds until they are at least a year old. We would be blessed and thrilled if Boston followed in his older brother’s growth-steps and could put on weight so quickly. We can’t really count on it because the side effects of congenital nephrosis include a lack of appetite and problems with malnutrition. Most babies have to be on a battery of supplements and formulas, sometimes even intravenously, but we would love to have the chance to try and breastfeed Boston and see if he will super-grow.
A lot of times the best match for a kidney transplant will be one of the parents. One of the sites we have been visiting is
www.cota.org, Children’s Organ Transplant Association. Most of the kids under the “kidney” link have received transplants from either their mom or dad. One of our prayers includes Brian or Sarah being a viable match for a transplant. Although a baby-sized kidney would be better than an adult-sized ones, the availability of a parent match is usually seized upon. Brian and Sarah have the benefit of both having the blood type of A negative, which is dominant, meaning all of our kids will hopefully have an A negative blood type as well. This should give us a great leg up for the transplant possibilities. For those who are wondering, Clark is out of the running to be a transplant candidate because (1) we wouldn’t put him through that and (2) even if we would consent to the testing, we couldn’t. Because the donation of a kidney puts you in a weakened state kidney-wise, he has to be of a certain age to consent to such a major surgery and we cannot consent on his behalf.
Whew! As you can tell, this is quite a bit for us to process. What we know right now is that Boston is doing great. Our ultrasound on October 1, 2008, told us that he is doing awesome. He is growing like a champ. He is topping the 90th percentile in size for his age. This ultrasound showed us that his kidneys didn’t look “bright,” but the doctor thought they looked “textured.” We will go back in four weeks for another sonogram. Most kids who have congenital nephrosis will have a couple of signs on the sonogram: (1) bright kidneys and (2) low levels of amniotic fluid. Both of those looked fine this time, and we will continue to watch for these signs.
Here are our prayers:
Our ULTIMATE prayers:
- That Boston will only have one broken gene, not two, and that he be born normal and healthy with the correct production of laminin.
- That we will be able to teach Boston how much God loves him and raise him to know Jesus as his Lord and Savior.
- That this experience will strengthen our relationship with God and be an opportunity for us to share our faith with others.
Prayers for the pregnancy:
- That Boston’s kidneys will continue to improve and show no sign of “texture” or “brightness” on the ultrasound.
- That the level of his amniotic fluid will stay normal in order to allow his lungs to develop and to reassure us that he does not have complications.
- That we will focus on the joys of each day and be reassured that “Today Boston is GREAT” and not borrow the unknown sorrows of the future.
- That every day we will “Live, Love, Forgive, and Never Give Up.”
Prayers if Boston is born with a disease:
- That he be healed completely.
- That he has a mild form of disease that does not affect his functionality.
- That he will have use of his eyes and not be blind.
- That his muscles will be strong and his brain alert.
Prayers if Boston needs a kidney transplant:
- That he will grow quickly and gain weight well in order to reach transplant size.
- That Brian or Sarah would be a match for the transplant.
We will be updating this site with new information about Boston and information about the possible disease. We will also be including songs and bible verses that have been impacting us, and prayers that we are lifting up.
Bible verse: Psalm 37:23b (New Living Translation) “The Lord delights in every detail of our lives.” This short verse reassures us that as God was makes Boston, he delights in every detail, including the writing of his genes.
I walked into the NICU and all of a sudden it struck me that this was not a place I wanted to be. Although they try to make it as friendly as possible, you don't have to be there for more than a few seconds to know that the babies here are sick. On the ceiling, part of which you can see in the picture, is the phrase "Wish I May, Wish I Might, Grant the Wish I Wish Tonight." It hit me that the wish these parents wanted granted was for their babies not to die, and that was overwhelming -- a parent's plaintive plea for their child to survive. All of the doors are glass for security reasons and so you are surrounded by room after room, bassinet after bassinet, of babies who are gravely ill. I teared up as I realized that Boston could be coming here and I had such a surge of protective mother instinct -- thinking "I don't want my baby to be here -- I don't want him to be sick. I don't want to have to wish that he would live." I am pretty sure that this aversion to the NICU will pass; after all, I want Boston to be where he needs to be in order to get better. But I was surprised how much it affected me.
Rubbing his right wrist against his mouth -- all tucked up.
Boston's right leg.
Posts
