Several Updates From July
We have had several appointments in July. In fact, we have pretty much an appointment or test per week for the next several months. I like to try to update after each appointment, but sometimes it is wishful thinking with everything else that we have going on! I am going to be creating a Facebook page for Elizabeth since we officially have a diagnosis. I will post quick updates there, and then continue to post more detailed information here on the blog. Here is a list of updates by department for the last half of July:
Genetics:
We had our long awaited meeting with Genetics about the results of Elizabeth's exome sequencing to look at her DNA for mutations that could explain her many symptoms. We had known for three weeks that the results were in, but it took a while to get an appointment to go over them. They would not discuss the results by phone. The results finally gave us some answers and diagnoses for Elizabeth. We knew at this point that whatever they found would be rare, but we had no idea how rare. Neither Jason nor I slept much the night before as we waiting in anticipation for the meeting with Genetics. We were able to go to the appointment together, and we are thankful that our Pastor Joe and his wife, Carol, were able to watch the kids for us, so we could go and be given the news together.
The first significant finding was that Elizabeth carries a rare copy of a genetic mutation for the AGRN gene for a diagnosis called Congenital Myasthenic Syndrome (CMS). CMS is a neuromuscular disorder that can cause issues with communication with nerves, muscles or both nerves and muscles. Elizabeth's form is called CMS with pre and post synaptic defects, which means that hers causes problems with both the nerves and the muscles. Her form of CMS is extremely rare, and she is the 8th confirmed case in the world with her specific genetic mutation of the AGRN gene causing CMS. There are approximately 7 billion people in the world, which makes her a one in a billion princess. There are other forms of CMS, some more rare than others. I'll discuss more information on the prognosis, medications, treatment options, etc. in the update for neurology.
Here is a link with some more information about CMS. It is pretty general information, not necessarily descriptive of all of the issues with Elizabeth's type of CMS, but you can get an idea of more detailed info if you care to read more:
http://www.mda.org/disease/congenital-myasthenic-syndromes/overview
The second diagnosis is called Nijmegen Breakage Syndrome. Elizabeth has a mutation of the RAD50 gene, which causes a different form than is typical of Nijmegen Breakage Syndrome (NBS). NBS causes an increased likelihood of cancer, developmental delays, immune deficiency, frequent infections, skin issues, failure to thrive, vision issues, and gross motor delays. Since there is typically another type of genetic mutation involved with NBS, a Radioactive Assay test was sent to a lab at UCLA for further investigation into Elizabeth's form of NBS. We have an appointment with Immunology on August 5th, and will be discussing this portion of the diagnosis in more detail at that time.
The first significant finding was that Elizabeth carries a rare copy of a genetic mutation for the AGRN gene for a diagnosis called Congenital Myasthenic Syndrome (CMS). CMS is a neuromuscular disorder that can cause issues with communication with nerves, muscles or both nerves and muscles. Elizabeth's form is called CMS with pre and post synaptic defects, which means that hers causes problems with both the nerves and the muscles. Her form of CMS is extremely rare, and she is the 8th confirmed case in the world with her specific genetic mutation of the AGRN gene causing CMS. There are approximately 7 billion people in the world, which makes her a one in a billion princess. There are other forms of CMS, some more rare than others. I'll discuss more information on the prognosis, medications, treatment options, etc. in the update for neurology.
Here is a link with some more information about CMS. It is pretty general information, not necessarily descriptive of all of the issues with Elizabeth's type of CMS, but you can get an idea of more detailed info if you care to read more:
http://www.mda.org/disease/congenital-myasthenic-syndromes/overview
There is no cure for either of the diagnosis, however there are treatments that will help to target symptoms. We have been told, though, that some treatments for the CMS will interact and cause complications with treatment for the NBS, and vice versa. So, we may have to determine which symptom is the most significant to treat at the time in order to avoid adverse interactions. Also, because these two diagnosis are so rare, we will often be making decisions about including her in research and clinical trials for medications and treatments not approved by the FDA in order to find treatments and medicines to help Elizabeth, to stop progression and to keep her stable. Those are bridges we will cross, conversations we will have, when those situations arise. We are glad to finally have diagnoses, but it is a lot to take in and process for us.
Pulmonology
Elizabeth had a follow up appointment in Pulmonology with Dr. Forno a few days after the genetics appointment. The follow up appointment went well. We are seeing less coughing now that she is no longer taking anything in by mouth. This tells us that many of her respiratory issues were caused by her aspirating during feeds. She is experiencing more stridor and wheezing when she breathes, and she has been taking some gasping breaths intermittently, this is likely due to the CMS causing issues with her respiratory function. So, we are going to keep an eye on that. We will likely be doing a sleep study in the near future to make sure that she doesn't need CPAP at night. As of right now, we are going to continue her inhaler and breathing treatment regimen, because she is showing continued respiratory progress and stability. We will follow up in six months, but that is likely to change with the increase in wheezing, stridor and the fact that we now know that her CMS can greatly impact respiratory function. All of this means that she will likely need to be followed more closely by Dr. Forno from a pulmonology standpoint.
Dermatology
Elizabeth had a follow up with Dermatology two weeks ago. The appointment was to check the status of her rash on her cheeks, to determine if the cream was working, and to discuss her sunlight sensitivity further. Her rash on her cheeks is improving, so we will continue with the cream that we have been using to treat it. The NBS diagnosis does cause issues with the skin, so we will keep an eye out for any newly developing rashes, etc. on her skin. Elizabeth is still experiencing a lot of sun sensitivity, so they gave us some samples of different sunscreen to try for her. We will continue to watch her skin, symptoms and will be following up with Dermatology as needed or in six months.
Dentist
Elizabeth also had her very first dentist appointment also two weeks ago. We went to Dr. Kobil in Butler, and it was great to see Janet Peter's friendly face there, as well. They were great with Elizabeth. She was very uncooperative with letting them look in her mouth, but they were eventually able to get a look and count her teeth. We brush her teeth with a little bit of water every day, since she can't have anything by mouth, we do not use toothpaste in case she would swallow it. Since her teeth looked very clean, we will just continue to do that. She may require some dental work simply because of her cleft palate, and if so, they will refer her to the dentists at CHP for treatment due to her complex medical issues. We will continue to follow up with Dr. Kobil every six months in the meantime.
GI
Last week, we had two appointments on the same day: GI and the long awaited Neurology appointment to discuss Elizabeth's CMS diagnosis. The GI appointment was spent discussing Elizabeth's continuous 24 hours-a-day feeds, her recent need for gut rest, and the leaking around her tube that has recently started to occur. Elizabeth is completely fed into her intestine through a J-tube, and recently she has been having episodes of formula leaking around the G/J tube site, hiccups, spitting up, and green output from her G-Tube site. She was recently put on "gut rest" last week, which involved putting her on straight Pedialyte instead of Pediasure, then transitioning her to a 50/50 combination of Pedialyte and Pediasure, all while continuously venting her G-tube site to get rid of gases, drainage, etc. This gut rest went on for about 72 hours, then her symptoms subsided, and we returned her to full feeds of Pediasure.
Elizabeth is continuing to gain weight. She has gained almost 4 pounds since we were discharged from the hospital in June, which is great. She is getting chubby cheeks, and chubby thighs, has a lot more energy, and we are seeing improvements in her language, movement and cognitive skills. It is truly amazing what adequate nutrition can do, and she is finally thriving. We are continuing her cocktail of GI meds, because they are working to keep her reflux controlled.
The GI doctor was concerned about her tube being misplaced, and so they made arrangements to send us up to Interventional Radiology (IR) to have her tube checked out. So, we went up to IR and they examined her tube. They determined that her tube was in place and was functioning properly. They suggested that since her rate is as slow as it can be for a 24 hour feed, that she likely has motility issues, and we should keep an eye on additional leaking around the tube site. I did let GI know, and they sent a message to GI as well, but I'm still waiting to hear about their plan. I am going to call again today to check in with them. We are following up with GI in two months. It was quite an eventful morning, as I was not expecting to be sent up to IR, but I was glad to get her tube all checked out while we were there.
Neurology
After our GI appointment, we had some time to kill. Elizabeth took a nap in her stroller, and I reviewed my notes, read a book and ate some food while we waiting for our second appointment. The last appointment that day was a long awaited appointment with the lead Neuromuscular disease doctor at CHP, Dr. Abdel-Hamid. It was recommended that we schedule an appointment with her once the genetic results came back. She is a leading expert of neuromuscular disease. In fact, she only sees patients that have neuromuscular diseases. I was looking forward to the appointment to gain some more info on how the CMS was going to continue to progress with Elizabeth, what kinds of treatment options there were, what to expect, what comes next, who else can we see, etc.? I had three pages of questions before I went into the appointment.
Dr. Abdel-Hamid was amazing. She will be following Elizabeth in the Neurology department now. She answered all of my questions, and many more that came up during the appointment. CMS is a progressive neuromuscular disease, and the earlier the onset the poorer the prognosis, and with Elizabeth's rare genetic mutation, and the fact that her type causes issues with both nerves and muscles, it is like a quadruple threat to her well being. She recommended that we get Elizabeth registered with the Muscular Dystrophy Association, because although CMS is not Muscular Dystrophy, CMS research and clinical trials are managed within the MDA. She also recommended that we take Elizabeth to the Mayo Clinic in Minnesota to see Dr. Engel who is a CMS expert. He has seen the other few cases with her genetic mutation, and he has seen and treated many others with CMS. Her secretary are helping me to register Elizabeth with the MDA and to get her an appointment with Dr. Engel. It is important to register Elizabeth to the MDA, so that she can benefit from being a part of the organization, can be informed of programs and research and clinical trials that apply to her diagnosis, etc. It is important that she get into see Dr. Engel for many of the same reasons. Elizabeth is the only case of CMS that Dr. Abdel-Hamid has ever seen with her specific genetic mutation. However, she has treated other children with other forms of CMS. Dr. Abdel-Hamid also mentioned that we would likely be contacted by other physicians, etc. now that Elizabeth is the 8th confirmed case of her condition. There will be researchers and physicians who want to include her case in research to learn more about this rare disease and genetic mutation.
We also learned at the appointment about different treatment options for symptoms. Again, there is no cure. There is not a medicine that she can take, or a treatment that can be given, that will magically change the mutation in the gene, and rid her of this neuromuscular disease. There are drug treatment options to help control symptoms, slow progression, and even potentially make her stronger in some ways. For example, one of the primary symptoms of CMS is that the symptoms are worsened by physical activity. So, the harder Elizabeth works, the more active she is, the more fatigued and tired her body becomes, which is exactly what we have seen and been describing to doctors all along. Some of the medicines, if they work for her, will help to reduce the fatigue brought on by activity. I mention, "if they work for her," because there are only a few medicines, and they are all known to be somewhat effective with the other more common forms of CMS. Also, since she is so young, she will be taking medicines for longer periods of time, and with that you have to worry about building tolerance, which makes the drug either less effective or can make it ineffective all together. Also, there are only a few drugs, and some of them are not approved by the FDA, and so are part of clinical research trials. Also, some of the medicines have nasty side effects, for example, the one drug is known to make you stop breathing as a side effect, and so they will not start you on that medicine unless you are admitted as an inpatient to monitor your reaction. So, we will have lots of conversations about medicines, weighing in the pros and cons, hoping that we find something that works for Elizabeth. One final barrier to the treatment options is that it needs to be in liquid form. At least one of the medicines is not available in liquid form, and this of course, is the first treatment option with the least amount of side effects.
We are hopeful that we will find a medicine that will slow the progression. We are also hopeful that this journey has led us to Dr. Abdel-Hamid. She is going to continue to follow Elizabeth as part of the Muscular Dystrophy Clinic at CHP. Elizabeth will no longer need to be seen in the Cerebal Palsy Clinic, because she does not have Cerebal Palsy, which is confirmed by the recent genetic results. We are also having muscle biopsies and nerve conduction studies done on Elizabeth on Friday, August 7th at CHP by Dr. Abdel-Hamid to get a baseline on how well her nerves and muscles are function, so that way we are better able to track progression of the disease. We will be following up with Dr. Abdel-Hamid every two months.
After the appointment, I joined a CMS support group, and I have actually located two other individuals with Elizabeth's specific mutation. Once is a 5 year old in Prague, and the other is a woman who lives in New Hampshire. I am so glad that I found the group, because already they have been a wealth of information, hope and support.
