Ronan the Great and the Case of the Missing Exons

Ronan the Great. Whose third or fourth word, after Mama and Dada, was "help." Obsessed with brooms and vacuums. Lover of trucks and dinosaurs, stuffed whales and stuffed puppies. Maker of messes. Taker of naps. Shrieker of shrieks. Blower of bubbles and patter of dogs. Lover of a big brother. He runs to greet him at the door after school. He sneaks into his room in the wee hours in hopes of waking him up to play. He is a man of mystery. He dumps out a bucket of matchbox cars only to put them all back in. He builds a tall tower out of blocks just to knock it down. He asks for a snack and then throws most of it on the floor, or feeds it to the dog. He both loves and detests snow. He repeatedly turns on the battery operated dinosaur, then cries when it dutifully roars as programmed until someone rescues him by turning it off. He is an observant child, and can sit quietly watching and listening for an impressive amount of time. Sometimes he can't stay still for more than a second. And now he is the center of another mystery. The mystery of the missing exons.

The mystery will be solved in about a week. Ronan and I will both have blood drawn. Mine will be tested to see if it contains the same mutation that Griffin has (a deletion of exons 60-62 on the dystrophin gene), and Ronan will have his CK levels tested. While we will have to wait a month to find out if I carry the mutation that gave Griffin MD, we will know within a day or two if Ronan also has it. If his CK levels are elevated like Griffin's are, we will know that he shares the mutation with his brother, and more than likely I have it too and passed it on to both of my sons. Let's just say I am a little bit nervous.

People get confused about this part. Why isn't Brian being tested? And if I have the mutation, why don't I have MD?

Amazingly, the introductory genetics class I took in college is making itself useful fifteen years later. When I read that Duchenne and Becker muscular dystrophies are "x-linked" genetic disorders two months ago (what feels like a lifetime ago) I actually knew what that meant.

In explaining Griffin's condition to friends, family and co-workers, I find myself giving mini lectures in human genetics. Here's a little snippet of genetics 101: everyone is made up of information stored in the form of genes on two chromosomes. Exactly what is a chromosome? I don't know, but that's where your genes are. Anyway, women have two x chromosomes and men have one x chromosome and one y chromosome. Women=xx and men=xy. This should sound familiar so far. When there is a flaw on a gene that is found only on the x chromosome (like the dystrophin gene), females have another x chromosome with a healthy gene to cover for the mutated gene. Males only have one x chromosome, so they have no way to make up for the problem. This means that boys get the full-fledged disease, girls don't. Since one of their x chromosomes is flawed, girls will have a lower level of dystrophin than normal, which can sometimes lead to mild symptoms. If a girl gets an x chromosome with the mutation, she can pass it on to her children. If she has boys and they get the dysfunctional x from her, they will get the disease. Since she has two x chromosomes, one healthy and one mutated, and will only pass on one of these to her child, she has a fifty-fifty chance of passing on the mutation. This is called being a "carrier." If Griffin's mutation is found in my DNA, we will know that I am a carrier and that he got his defective x from me. Where did I get it? Either my mom is also a carrier and passed it on to me, or the mutation arose randomly in the egg that I developed from.

If I am not a carrier, it is possible that Griffin's one and only x chromosome has a spontaneous mutation that happened only in the egg he developed from. A third possibility is that I have what is called a "gonadal mosaic," which means that I don't have the mutation, but some percentage of my eggs have a mutated x. If this is the case, I will not show up as a carrier because the mutation isn't in my DNA. Currently, the only way to diagnose gonadal mosaicism is if a woman who has been found not to be a carrier has another child with Duchenne or Becker. As if this disease weren't mysterious enough already.

Ronan has zero symptoms of muscular dystrophy at the moment. He walked a little late, at 15 months, but that is still well within the normal range, and he was an expert crawler. Griffin was still not walking at 18 months, which was our first real clue that something was amiss. Ronan often stands up from a squat without using his hands. He tries to walk up and down stairs, and sometimes even alternates his feet. He is as close to being able to run and jump as Griffin is, despite being 3.5 years younger. No worries about him, then, right? Oh, but remember that this disease is nothing if not mysterious. Mystery is its middle name. Duchenne Mysterious MD. Every single case of Duchenne or Becker progresses a little bit differently. Even brothers, who have the exact same mutation, can manifest symptoms in wildly different ways. Some have symptoms nearly since birth, like Griffin, and some don't show any signs until they are 3. Why? No one knows. Probably it's just that every body is a little bit different. Some of us might have more of the other (non-dystrophin) proteins that protect muscle than others. Some of us probably regenerate muscle faster than others. For whatever reason, every patient handles the lack of dystrophin differently.

Our own family's mystery will be solved soon. Stay tuned.

So, how is Griffin?

Whenever I give someone "the news," one of their questions is usually, "does he know?" The answer is yes, and no.

Griffin doesn't know his prognosis, and even if we were to tell him I don't think his five-year-old brain could comprehend what it means. He does know he has something called muscular dystrophy and that it makes his muscles weak and so that is why he has to go to the doctor and do PT and stretch every day. I know that children often know more than they let on, and that they sometimes appear to be busily working on a lego construction or a coloring book or a play-doh sculpture, but are in fact intently listening to what the adults are saying. So I think it is possible he knows more than we think he does. He has been saying he doesn't want to grow up, that he wants to be a little boy forever. I wonder if he has an inkling that life will get more difficult for him as he gets older, or if he is just entering that period of angst so many children have when they realize they will one day be adults with responsibilities they can't begin to comprehend, but know are coming. Every so often, I remind him that if he hears me or his dad talking about something with his teachers or to his doctors or to anyone else, and he has any questions about anything he hears, it is OK for him to ask and we will always answer him. So far, when I encourage him to ask questions, he usually just asks me what's for dinner or if it is movie night or if he can have a piece of candy.

Another common question is "how is he doing?" Right now, pretty great. Other than being a little slower than his peers, he is like any five year old. He had a physical therapy evaluation two weeks ago, and it was encouraging. Both the therapist and his neurologist think he still has another couple years of gaining strength, and that he should be able to make some more gains. The physical therapist will be focusing on coordination and flexibility, and is optimistic that she can get him pedaling a bicycle and possibly even jumping or at least hopping. I hope she is right, because both of these are things Griffin would love to be able to do. He has very tight hamstrings, and we have been doing stretches every day since his physical therapy evaluation. This is important to keep his muscles as flexible as possible and avoid the risk of contractures later in his life. Griffin is not particularly happy about the intrusion into his activities that having to stop for stretching imposes, but he has been doing them and usually happily chooses which stretches he wants to do. We also got him a foam wedge and a scooter board (remember those wooden squares with little wheels on them from gym class in middle school?) that help with stretching and are also fun to play with. So far, so good. We are making the adjustments we need to make and trying not to think more than a few months into the future.

There are times I am kept awake at night thinking about how his calves seem to be developing by the minute, stretching against his skin in a last ditch effort to make up for the weakness in his thighs. Despite the doctors' consensus that his symptoms are mild and that he still has a few years of strengthening before he starts to weaken, I find myself watching him every time he stands up to see if he puts a hand on his thigh or not (Gower's sign). Sometimes he does, sometimes he doesn't. I also find myself watching Ronan, breathing a sigh of relief when he pops up from the floor without using his hands at all, or alternating his feet when he steps up stairs, and then wringing my hands the next minute, when he stumbles over the edge of the carpet or pushes his hands against the floor to stand up (totally normal for an 18 month old, by the way). When we have the genetic test results back for myself and Ronan, I will be very relieved if (when!) his results are normal, but a tiny part of me will feel just the slightest bit sad, knowing that Griffin will be alone with this in an otherwise healthy family.

For Griffin, life goes on as it always has, and is even, dare I say, a bit better. His birthday was quite the event this year. It felt like a wedding weekend, with family descending on our household, days of cake-baking and party preparation, several birthday events, a party complete with a puppet show, treasure hunt and 16 kids in attendance (our biggest birthday party turnout ever). We've made extra efforts to go out and do fun things as a family, and are planning vacations that we would have put off much longer, or possibly never have taken at all. It's been pretty fun around here lately, I will admit. In part, it is an attempt to distract ourselves, and in part it is because everything feels like it should count more, everything should be the best and funnest it can be. To my plodding motto of "one day at a time," I will add a more energetic "carpe diem."

Life is worse in a lot of ways, but also better in a lot of ways. Still, I would give up all the good stuff to have my normal, healthy child back.

Welcome to Holland

Mountains and Egyptian Rivers

I feel like I can't write any more blog posts without first saying how blessed I feel to have so many people, from close family members to near-strangers, rallying around us and offering kind words, help in many forms, from childcare to making us soup, providing shoulders to cry on and ears to listen, putting together MDA Muscle Walk teams in Griffin's honor, making donations to PPMD, and more messages, texts, emails and phone calls than I can count. If I tried to list all of you here, it would take up pages and pages. Thank you, all of you.

One of these helpful people is an old friend who was one of the first people I told about Griffin's diagnosis. She has two children with a different serious health condition that can be life-threatening if not managed carefully (she knows who she is). She told me that one rule she has is to "never, ever think about them dying," which at first sounded an awful lot like denial to me. Short of a  medical miracle, my son has no shot at a normal or full-length life. I have no choice but to think about him dying, because I know I am going to have to watch that happen at some point, far sooner than I can accept. This week, though, I realized that I discarded her piece of advice a little too hastily.

There are moments when I want to climb a mountain with a megaphone and blast this into the atmosphere: "What kind of ridiculousness is this? I thought I had a healthy child! He is missing one stupid protein and this is what happens? And there is NO CURE??? This is a cruel joke. It's not fair! Everyone else gets to keep their kids! ONE protein! Just make a batch of it and pour it into him. WE NEED SOME DYSTROPHIN UP IN HERE! Yesterday! People have been watching their kids die from this for centuries, and we can't figure out how to fix it? ARE YOU KIDDING ME WITH THIS SH*T?" If anyone had told me even three months ago that I could survive having a child diagnosed with a terminal illness, I would have thought that person was crazy.

Sometimes, though, what seems unsurmountable can be surmountable if you just take it one step at a time. Anyone who has ever climbed a mountain knows that it is a terrible idea to stand at the bottom, staring up at the peak, worrying that you might not have the strength to make it to the top. It's paralyzing, and the first step toward failing to reach the summit. My metaphor breaks down a little bit here, because the fact is I never want to reach the "summit" of this particular "mountain." I want to wander around in the foothills forever. But I think you probably get my point. Griffin has several more strong years before he starts to weaken. I can spend these years thinking about his future, worrying about what it will be like when he can no longer walk, imagining his untimely death, wondering what life will be like without him, and ranting angrily into a pretend megaphone. Or, I can spend these good years having as much fun as possible, finding ways to make sure he gets to do the things he wants to do most, helping him to do the things he loves and to use his talents and abilities. Most parents would say that what they want most for their children is for them to be happy. What I want most for Griffin is for him to be happy, and I owe it to him to put aside my fear and my anger and my sadness and be happy with him.

In order to do that, I will do as my friend suggested. For the time being, I will never, ever let myself think about him dying. Her point, I realize now, was not that we should live in denial. It was that we should not to let the bad things that could happen, or even the bad things that almost definitely will happen, keep us from being happy and enjoying life. Eventually, I know I will have to start up the steep trail that leads to the peak. But until that day comes, I will soak up the sun, smell the flowers, listen to the birds and relax by the river (and no, not the one in Egypt).

Internet Research and Birthdays

Today, Griffin's neurologist called to give us his genetic test results. He has a deletion of an exon in the gene responsible for making the protein dystrophin. Dystrophin is part of a group of proteins that protect and strengthen muscle fibers. Without enough dystrophin, muscles are damaged from everyday use. Over time, muscles degenerate and atrophy, and are replaced with fat and scar tissue (fibrosis). This leads to dependence on a wheel chair and eventually death from cardiac or respiratory problems.

Griffin's deletion is one that can lead to either Duchenne MD or Becker MD. In Becker, patients make some functional dystrophin but not enough to fully protect their muscles. The end result is the same as Duchenne, but its progression is generally slower.  To find out if Griffin has Duchenne or Becker, we will have to do a muscle biopsy to find out if he has any dystrophin in his muscles. If he has more than trace amounts, he will be diagnosed with Becker. Otherwise, he will be diagnosed with Duchenne. Since he already has symptoms, even if he has Becker, it will be a more severe version and it doesn't make that much difference which it is.

Do I sound like a know-it-all? Well, I admit I looked it all up on the internet. Every doctor we have spoken to and also some other well-meaning advice givers have cautioned us about looking stuff up on the internet. You will just scare yourself. You will find lots of questionable and misleading information. I always nod like I understand and will dutifully not look up anything on the internet, but it's just a facade. Here's the thing: I am going to look up everything the doctors say to me on the internet. I am going to scour the internet for the latest news on clinical trials and the latest treatments for this horrible disease. 100% of people diagnosed with Duchenne are children. They are dependent on their parents to be their advocates. I need to be able to ask my doctor informed questions, and I know his doctors don't have time to sit around reading scientific journal articles and clinical study reports all day long. They do their best, but their first priority (and rightfully so) is taking care of their patients. You know whose job it is to know everything there is to know? MINE. I want to be sure I have the most up to date information so that I can help guide his care and make sure it is the best it can be. From what I can tell so far, parents of children with MD become experts in the disease very rapidly. We are our children's advocates and protectors. In order to do this effectively, we must become know-it-alls.

The source of a lot of my information as well as the much-needed sense that I am not the only person to be in this most unfortunate circumstance is the Parent Project Muscular Dystrophy website. This organization was founded by a woman, Pat Furlong, who has two sons who died from Duchenne. She knows exactly what it is like to be a parent to a child with a serious illness before there was the internet and before there was social media. It was isolating, and hard to find information about her sons' disease. When faced with this diagnosis, we as parents want to feel proactive, and like we have some kind of leverage. Knowledge is power, as they say. So Pat Furlong and some other parents of children with Duchenne started the Parent Project to provide parents with information, including the latest research on and treatments for MD, to help connect parents of children with this condition with each other and to give parents the tools to participate in fundraising for the most promising drug research.

Griffin's fifth birthday is January 18th. In honor of his birthday, I shamelessly suggest that you consider a donation to this organization. It is truly providing parents with the tools and knowledge to be their children's best possible advocates. I can add this organization to the list of things I am grateful for. Making a donation right now will help PPMD develop a "Duchenne Superhighway" that will help speed research into the most promising drugs. One of his doctors said, "There are hundreds of drugs currently in the process of development…we just need one of them to work." A miracle just might be within our reach. It is possible that a donation to this organization will help to ensure that Griffin has many more birthdays to come.

In the meantime, life goes on. For his fifth birthday, Griffin lost his first tooth!