Our Happy Girl

I don't have time to write a long entry today, but I thought I would post a video of Becca from a few weeks ago. 

Becca really is happy most of the time and it is so contagious!  We sure love her.

Rett on the News

If you are interested in learning more about Rett Syndrome, KSL posted the story that ran last night on their website: http://www.ksl.com/?nid=148&sid=8649182. The doctor that they interviewed (Dr. Rope) is Becca's geneticist.  They talk about some interesting stuff!

Becca's Walker

We recently borrowed a walker from Becca's physical therapist and I know some people are interested to see what it looks like.

She tolerates it pretty well. We are working up to 30 minute increments and we're at 10 minutes so far. I don't force her too hard because I don't want her to hate it. She's starting to move a tiny bit in it, but is not taking steps yet. We are grateful for another way to do physical therapy with her and hope that it helps her!

Seizures?

We've wondered for a while if Becca has had seizures. It's a common problem for girls with Rett, although they can be hard to recognize sometimes -- even with an EEG, since the results are commonly abnormal in general for Rett cases. In Becca's case, we suspected she had them in her sleep, and that we may have actually seen some when she got startled awake. In the nighttime if we ever had to sneak into her room and accidentally made a noise, her eyes would pop open, and a second or two later her arms and legs would come up off the bed and start shaking/tremoring for fifteen seconds or so.

We asked the neurologist about it, and she assured us it was just part of her ataxia, and that when she woke up her muscles were just spasming because she didn't have control of them yet. That's what we wanted to hear, since we really didn't want her to be having seizures. It seemed to make sense, too, since she could look around and wasn't holding her breath when it was happening, and someone somewhere told us people won't look at you when they're having a seizure (not so sure if that's true anymore, but that's what I heard at the time).

Anyway, now I'm not so sure she wasn't having seizures. I think we've already mentioned the two separate mornings when Becca woke up a complete noodle, just very worn out and moany. She'd mostly recover after half an hour or so, but it would mess up her development somewhat, and we were really worried that those actually were seizures, so we talked to the neurologist again, and ended up getting a 48-hour EEG scheduled.

Becca had one of her shaking spells while hooked up for the 48-hour EEG. We pushed all the buttons and everything to make sure they got it recorded, and one of the nurses came in right after and said it looked like they'd recorded a seizure. Next morning the neurologist stopped by and said that wasn't true. She said Becca's EEG was abnormal in general, and while everyone agreed that the shaking looked just like a seizure, the EEG didn't show anything to convince them that it really was a seizure. Even still, she decided to put Becca on Keppra in case the other two events really had been seizures.

Fast-forward to now. Becca doesn't do the shaking thing in her sleep anymore. At all. Her ataxia is just as bad as it's ever been (we were playing piano together today and I had to hold her just right or she'd shake at her trunk and lose control of her arms), so I doubt that she's just "better", but I can't get her to shake in her sleep like she used to. I've actually been trying for a few weeks to get a video of it to post, because we can't seem to get a definitive answer on what it is, but she's actually a really deep sleeper now. I just went into her room, flicked on the light (she flinched at that, but that was all), made some really loud noises, and even sat her up in bed, but she wouldn't wake up at all. I finally got her to open her eyes, but there was no startling into shaking like there used to be.

I know there's probably confounding factors. Maybe Keppra makes you sleep more soundly or something, or maybe she's just moved out of that phase. But I really can't help but suspect that those were little seizures she was having. The last time we spoke to the neurologist (Dr. Benedict) she said she wasn't convinced that the episode they recorded wasn't a seizure, and I'd probably say the same thing. Especially since she hasn't had the little drops in development that she used to have.

It's probably worth mentioning that Becca doesn't breathe well, especially when she's asleep. She gasps sometimes when she's awake, and when she sleeps she tends to take little tiny breaths, stop breathing for a few seconds, then take a deep breath. I know that's also not uncommon with Rett (and Paula actually breathes infrequently when she sleeps, too), but there you go.

Anyway, the moral of the story is we don't actually know if Becca's ever had a seizure. We're pretty sure she has, but nothing's been officially observed. And we wonder if maybe those small shaking episodes were seizures as well. The good news is that Rett cases tend to have fewer seizures as they get older (although by older they tend to mean adolescence or beyond, not two and a half), and of course that whatever those shaking spells were, they're gone now -- can't say as we were the biggest fans of them, whether seizures or not.

Becca's Story

Since we want this blog to be a record of our journey with Rett Syndrome, I thought it would be a good idea to record a little bit about Becca's life so far.

March 20, 2007. Rebecca Jane Whitmer joined our family. The second I laid eyes on her I knew she was special. I can't really describe it in words. It was just a strong feeling that I was extremely blessed to have such an amazingly strong and special girl as a part of our family. The first part of her life was quite uneventful. She was a healthy, happy baby and very content most of the time. Her only problem was that she didn't know how to suck when she was born. It took her until she was two months to learn to nurse. Looking back on it we now realize that she was a floppy baby. She learned to lift her head a little bit later than other babies and it sure seemed a lot harder for her.

By five months Becca was really good at rolling from her tummy to her back and she wasn't consistant at rolling from her back to her tummy until she was seven months. But she was quite the roller.

The first time we really started to worry about Becca was at around 9 months. We would try to get her to sit and after a few seconds she would fold in half and then she couldn't get back to sitting. At around 11 months she wasn't really any better so we signed her up with the early intervention program. She started up with physical therapy right away and within a month we saw a big difference. She could get herself back up to sitting if she folded in half. Also around this time we noticed that when Becca would get startled awake she would shake really bad (looked like arm and leg convulsions). We didn't think it was a seizure because she would look us in the eye when it happened, but other than that, it looked like it could be a seizure.

Around this same time Becca had her first of many tests. She didn't like (and still doesn't like) to put weight on her right leg. She had an ultrasound of her hips and everything looked great and normal! Her second test came when she was about 14 months. The doctor referred her to a neurologist (Dr. Benedict) at this time and she recommended that we get an MRI to make sure nothing was wrong with Becca's brain. Once again, completely normal!

Next on the neurologist's list of things to try was an EEG. This test would be done when Becca was asleep and would show us if she was having seizures (at least during the test anyway). This test came back abnormal, but there was no actual seizure activity. So, once again, no answer. It only could tell us that Becca may be prone to have seizures. At this point, Dr. Benedict was almost positive that Becca had Angelman Syndrome. We definitely didn't agree. But, Dr. Benedict referred her to a geneticist (Dr. Rope) which we thought was a good idea.

Around 18 months Becca started figuring out how to get up to sitting all by herself! We were so thrilled! She would get up on all fours and then push up to sitting from there. This was a huge improvement. I remember that one of the most exciting things for me was to see Becca sitting up when I went to get her from her crib. But it was sort of bittersweet, because her shaking was getting worse. She would shake whenever she felt unsteady or got scared.

At 22 months we took Becca to see Dr. Rope. He was almost 100% sure that it wasn't Angelman Syndrome. Yay. But, he was also not convinced that it was anything genetic. He told us of a few tests he would do if he were to do testing. But, he didn't want to right away partly because it's harder to get insurance to cover at that young age and partly because it's easier to diagnose when they're a bit older. Besides, he thought it was neurological. So, we were sent back to Dr. Benedict with the idea that we would come back to see him in a year and at that point do testing if things hadn't improved. Dr. Rope also told us to contact him if Becca were to ever be admitted to the hospital. Apprantly, insurance will pay for some genetic testing if she were in the hospital. So silly.

At about 24 months Becca started crawling! Not like crawling all over or anything. It took her a ton of motivation and prompting to get her to crawl to a toy. But, she was moving a little more and playing in kneeling position. We were so excited to see these little improvements.

Things were moving along with not much improvement. We had noticed that Becca had started doing this patting motion with her hands basically all the time. She wasn't able to use her hands to pick up small things anymore (no more self feeding). Also, her shakiness had gotten quite a bit worse to the point that it was hard for her to get to her toys and play with them without falling over. She was still putting everything in her mouth and biting everything she could get her hands on. We attributed this to teething (2 year molars are brutal). But it's not like this was a sudden change. It had been quite gradual, so we didn't notice it right away.
Then one morning (about 26 months) Becca had slept in quite a bit later than she usual does. Then I heard her crying in a different way than I had ever heard her cry. It wasn't really loud, just a soft really sad cry. I went to get her and when I picked her up I noticed she was really floppy. But, I had to nurse our other child so I placed her on the floor in front of me and figured she just had to wake up. When Brian came out and picked her up she was like a wet noodle. He could hardly hold her because she was just slipping through his hands. Needless to say, we were really scared. She was just laying there not moving and when we would try to get her to sit up she would just moan. I gave her a drink and just let her lay there while we tried to figure out what we would do. And then, about a half hour later, she was fine. Not 100% back to normal, but she was moving around and acting pretty much like she normally does.

We luckily got an appointment with Dr. Benedict that afternoon. She told us that it sounded like she may have had a seizure before I went in to get her. But what she was most concerned about was that Becca seemed to be doing worse. So she had us schedue her to have another MRI and EEG the following week. And the results from those tests came back exactly the same...normal MRI, and abnormal EEG with no actual seizure activity.

With those results, Dr. Benedict decided it was time to come up with a reason for Becca to be admitted to the hospital so that she could be tested for a couple genetic disorders. Dr. Benedict had her admitted for a 48-hour EEG. While she was there she had a couple genetic tests one being the test on the MeCP2 gene (Rett Syndrome). She also had an eye exam and a swallow study. Both were normal. Of course.
That brings us to August 25, when we received the results telling us that Becca has Rett Syndrome. I'm sure I will never forget what it was like to receive that news. It was such a strange mix of relief and complete devastation. We had been wanting to know what was wrong with Becca for all this time and yet, I couldn't help but have a small part of me feel like I didn't want to know after all. But, we take it one day at a time. We have our hard days and our easier days, and I suppose that's how it will always be.
I had a lot of fun putting together a slideshow of Becca's life so far. Becca has always been such a beautiful, happy girl. I sure love her.

Official Genetic Results

Well that was an interesting experience. We got a phone call last week with the official results of Becca's MECP2 tests. If you recall, before they told us they found something abnormal on Becca's test, but weren't sure what it was and they wanted us to get tested to confirm. When we finally got the call about Becca's test, Dr. Benedict (the neurologist) just said the test came back positive for Rett. She didn't say anything about the questionable-ness of the test, and we weren't entirely sure she got the final results instead of the intermediate results. Dr. Rope, the geneticist, called a few days later to set up an appointment to talk in more detail, and when we met with him we asked for clarification on our test results. What he said is that they asked for our tests for an independent study they were doing to double-check that there wasn't a correlation between parent and child in Rett cases or something like that. He said it was kind of inappropriate for them to not tell us that up-front, but at least we got tested for free and now know that Paula isn't a carrier.

Dr. Rope talked about a lot of stuff that I found interesting, and I thought I'd share. Keep in mind this is what I understood, so it's not necessarily 100% accurate, but it's probably more than you ever wanted to know anyway, so whatever :-).

The MECP2 gene, which is linked to Rett Syndrome (and some other issues, like autism and lupus), has four transcribed regions (exons), with exon 4 being the largest, which are involved in the process of generating the MECP2 protein. Mutations in one or more of the MECP2 exons can result in a malformed MECP2 protein and a common set of side effects known as Rett Syndrome.

In Becca's case, the mutation is on position 403, where she has a G nucleotide instead of an A in one of her X chromosomes (c.403A>G). Position 403 is part of the methyl-citosine-binding domain (MBD), and is on exon 4 which starts somewhere around nucleotide position 390 or amino acid position 130. This mutation is on the rarer side, 2 cases in 424 for the study I saw.

As a result of the mutation, the structure of the protein is altered because an amino acid is changed from lysine (AAA or AAG) to glutamine (CAA or CAG) (p.Lys135Glu or K135E, although if you search for K135E you run into a bunch of articles on Werner's Syndrome, which is this weird disorder where you age faster than normal). Lysine is a small, neutrally-charged amino acid, while glutamine is much bigger and negatively charged. As a result of the change, the protein can't 'fit' where it would have before, which causes problems. Dr. Rope said a few times that while the MECP2 mutation is a cause of Rett Syndrome, he thinks it's not the only cause, and that it's actually something that happens farther 'downstream', which is why some people test negative for Rett genetically with a positive clinical diagnosis.

Anyway, because all of this happens on the X-chromosome, it's not active in all cells. On a guy the X-chromosome is always activated, so an MECP2 mutation would affect every cell, which is why the only real male Rett cases have other problems (like Klinefelter's, where they have an extra chromosome, XXY). Since each cell only activates one chromosome, not all cells will have an active MECP2 mutation, and the ratio of mutations apparently relates to the severity of the disorder. X-inactivation is supposed to be random, which would put it at 50-50, but there can be reasons for it to not be completely random. Because Becca's case is somewhat abnormal and on the milder side, the assumption is that she doesn't have as many mutated cells as the common Rett case.

Oh! I just figure out what this lab report was talking about! The report said, "K135E was previously reported in several patients with classic Rett Syndrome; however, parental studies were not performed to confirm de novo occurrence. Another study found that K135E imparied the function of the MeCP2 protein." I didn't figure out until a minute ago that K135E and the Lysine-Glutemine problem were the same thing (although I'm still not sure what the 135 means in that... lemme know if you do!). So from that and Dr. Rope's comment, it sounds like the folks at ARUP are trying to show that the K135E mutation is not inherited ("de novo" mutations are new mutations, not inherited).

I actually thought all of that was really interesting. Maybe just because it's my daughter, I don't know. But none of it really helps in knowing what to expect for Becca's future. We did ask those questions of Dr. Rope as well, although he didn't have as good of answers. It's not his fault or anything, there's just not as good of answers to give. Andreas Rett first describe the syndrome in 1966, and since then there's been studies and things, but mostly on a clinical level. The genetic link wasn't discovered until 1999, so there's not really a lot to go off of. The cases that have been studied are those that matched the common case (which Becca's doesn't), and were diagnosed without genetic testing (which Becca wouldn't have been), so it's hard to say.

I'm still doing a lot of reading and studying on typical Rett (they call it RTT, I guess because that extra "e" in there was just too much to handle), and I don't know a whole ton more than I did before. I've been doing most of my looking on a technical level, though (interestingly enough, the report we got back from ARUP on Becca's lab results cross-referenced a couple papers on Rett, and they were the exact same ones I kept finding in my searches... I couldn't read them because I haven't paid for the journals, but maybe I can get to them on campus or something...). I'll start looking more normal places now for more general information.

Anyway, this post is totally just for the curious -- and in reality, probably just for my own benefit in the future. I assume this blog will change somewhat since we now have a diagnosis. Paula and I both agree that we'd still like to keep this blog going, in case it can be of use to someone else trying to figure out their own diagnosis or whatever (plus there's plenty more we'd like to share about Becca than we feel we can do without overloading the family blog), so stay tuned :-).

Eye Exam

When Becca went in for her 48-hour EEG, she had an eye exam as well. The eye doctor saw that her optic nerves were pale and wanted to schedule her for a full eye exam. This would involve using anesthesia so that they could easily get clear pictures of her eye.

This happened last Thursday and I'm happy to report that the day went very smoothly. Here's dear Rebecca all ready in her hospital pajamas. PS- They really should get new pajamas.


You can't tell from the pictures, but she was in very good spirits for the whole day. The exam took about a half hour and then we had to wait a little while after that before we got to see Becca. When they brought us in to the recovery room Becca was still in very good spirits and it was almost as if nothing had happened. I was so grateful because when she was put under for her MRIs she had a really hard time waking up and was unhappy for a day or two.

The results: 100% completely normal! They didn't tell us until after the fact that part of the reason they were doing this test was to see if she has something called Batten disease. I think they chose not to tell us ahead of time because it's a very depressing and fatal disease. But, well, no worries because everything was normal. The doctor even said that when they got a good look at her eyes he saw that the optic nerve wasn't even really pale (apparently Becca wiggled her eyes a lot for the other exam). So yeah, no new clues into our little puzzle girl, but we never mind getting normal exams! It's always nice to report good news.

Sister Golden Hair Surprise

One thing that nobody's ever been able to find a good reason for is the state of Becca's hair. It's really curly, which I think she gets from me, and she tends to get a bit of a mullet because she spends so much time on the floor still; there's a swath in the middle of the back of her head where the hair never gets long because she's always laying on it... just like any kid that still spends a lot of time on their back.

But that's not the issue, that all makes sense. The question mark is that Becca's hair is still really fine. At least I think that's the problem. It seems like little babies have much finer hair than adults, and it gradually gets coarser or something. But Becca's hair is still really really fine, and hasn't grown in very thick, either. Although the thin thing might be because it comes out really easily. She usually loses a bunch if we put any ties in her hair. One time she was playing with her cousin Logan and he came over and yanked a whole clump of hair out of her head. She didn't seem to mind at all!

We've mentioned it to the neurologist and the genetecist, and they both seemed to dismiss it -- or at least, not bother addressing it in front of us. Sometimes it's hard to tell if doctors really hear you or not. When we mentioned it to Dr. Savage she said, "I assume she's had her thyroid checked." We said, "uh, no..." So we got that tested, since apparently that's a common cause of hair loss. The first time they tested her thyroid, it came back just slightly outside the normal range (now I can't remember if it was hypo or hyper... should have written it down before), so they tested it again and it came back normal that time.

The only reason I even bring this up is because none of the likely candidates for a diagnosis (Angelman, Rett, etc.) seem to list anything abnormal about hair in their list of symptoms. Nobody's ever said "oh, that's normal for kids with..." any of the possible problems Becca's got. So maybe it's a red herring, maybe it's completely unrelated, or maybe somebody somewhere will say "does her hair fall out really easily?" and we'll say "yes!" and they'll say, "well, then obviously is Kerbsmilter's Syndrome" or something like that.

I guess more importantly, because Becca's hair can't seem to get very long, we're at a complete loss for what to do with it. Most days she looks like Cindy Lou Who (or maybe Medusa) with her unruly curly locks. We've recently started putting a little pomade in it so at least the locks kind of clump instead of looking like a complete mess, but we'd love to hear any thoughts anybody has on what to do with this girl's hair.

MECP2 Results

Paula got a call back from Primary Children's yesterday about the results of Becca's MECP2 test. That's a test for Rett Syndrome, by the by. Dr. Rope called himself, which was nice of him, and explained that they actually did find something abnormal on the MECP2 gene -- but he said it's something they've never seen before. Sounds like Becca, doesn't it?

Anyway, what they want to do next is bring me and Paula in and run the same test on us, just to see if there's anything abnormal on our MECP2 genes. If there were, then it might actually be nothing, since it's not doing the same thing to us that it's doing to Becca -- and even if there were it could still be nothing, but it also might be a hint into what's going on. Maybe. We'll let you know how our tests come out.