Tuesday, August 6, 2019

Nonverbal...no problem!

Every so often I have a dream where I’m talking to Emelyn. I wake up not remembering what we talked about, just that we were talking. This is a common dream for parents of children with DDX3X. As we’ve met DDX3X families and researchers we’ve learned that girls affected with DDX3X have about a 50 percent chance of developing spoken language. (As more children, and even adults, are diagnosed, this statistic could change.) At six years old, Emelyn is completely nonverbal—no “Ma” or “Da,” nothing. Don’t get me wrong, she’s very vocal, especially when she’s happy, but words just aren’t there. Emelyn falls in the 50 percent of girls with DDX3X who, for whatever reason, have a brain development that renders them unable to form and speak words.

The lack of meaningful language is likely one of the most challenging aspects of caring for Emelyn—hence my mind’s need to serve it up in my subconscious. We’ve come to recognize the obvious clues along the way about what Emelyn wants to tell us…like when she takes one book from your hand and replaces it with another, “Ok, clearly you didn’t want to read that book.” Or when she gives you that you-just-made-my-day-smile after you sing her favorite song. But beyond gestures and smiles, we are limited without spoken language.

Like many parents of children with DDX3X, we've struggled through multiple speech therapists, trialed countless AAC apps/devices, and spent hours trying to develop echoics...and still, nothing. About two years ago when Emelyn was four years old, I decided to use ABA principles (starting with hand-over-hand and eventually fading to near independence) to teach Emelyn the ASL sign for "read." I chose "read" because books are highly motivating to Emelyn and I knew she'd work for books. By the end of the weekend, she would hand me a book and sign "read." From there we learned other motivating words like "eat" and various other food-related words (cracker, cereal, thirsty, etc.), and it's taken off from there. At this point Emelyn knows 100+ words in ASL—probably more than we know since so many of us teach her different words (the internet is the best teacher—thank you Signing Time and SignSavvy.com).

Our biggest struggle is fine motor skills. Emelyn can’t precisely sign many words making several words look very similar, such as milk and potty. And certain words/letters are still beyond her ability—for example, she can’t isolate her pinky finger to form “i,” “j,” “y,” or “yellow.” Despite those challenges, we've seen huge strides as we continue to work together to learn and perfect signs. It's a labor of love that is giving us a window into Emelyn's thoughts, needs, and desires. She is so proud of herself and we are amazed at just how smart she is.

Sign language has given us a better glimpse into what Emelyn is capable of. For the last couple of years her ABA clinic has been working on color matching with Emelyn. It’s an exercise where the learner attempts to match two colors together, such as putting a blue block into a blue cup. And for two years, she’s struggled with this seemingly simple exercise. In our effort to learn new signs, I learned to sign the book Brown Bear, Brown Bear by Eric Carle. She quickly, probably more quickly than me, learned the signs for all the colors and animals. And while the color matching exercise is still a struggle, ask her to label colors and she can do it with ease (except yellow). It’s the same with animals. While most kids learn to first point to label an object, Emelyn still struggles with that skill. However, if I point to an object and she knows the sign, she will promptly label that object with the correct sign. She’s recently demonstrated a knowledge of more than half of the alphabet as well—it’s been a pleasant surprise and keeps us on our toes.

A recent text message from Emelyn's
physical therapistthey've been together
for six years. There is nothing but love between
Our children with DDX3X learn differently than typically developing children and I'm just so grateful that we're figuring out how Emelyn learns. For all of those who are struggling with language—as we were just two or three years ago—please know there is hope for your daughter or son. Keep trying new things and keep believing in her/him—and yourself!

Saturday, December 29, 2018

A look back at 2018...another year of hope

I can look back on Emelyn’s first year and remember the heartache of missed milestones and the fear of an unknown future—for her and for us. At our first Christmas, Emelyn was nine months old. While other nine-month-olds were pulling to stand on new toys, babbling away to goofy children’s books, and eating wrapping paper, we had one wish for Emelyn—that she would soon have the ability to hold her head up. It was a simple Christmas wish, yet one that seemed so far away. Emelyn would turn one the following March and still lacked enough head control to adequately hold her head up. To say it was a tough year would be an understatement. We spent that first year grieving the loss of the child we had anticipated would join our family. In our mind, Emelyn was a child who would meet milestones like walking and talking just like her peers. This is what we each anticipate when we initially find out we’re pregnant. We are immensely grateful to have Emelyn in our lives—we were then and we still are today, but the reality is, she was not the child we dreamed of.

Fast forward five Christmas’ later and Emelyn has many more missed milestones and her future remains fuzzy, but something has changed. Our grief has been replaced with hope. We have hope that tomorrow will be better than today—even if it’s such a tiny improvement that it can’t be seen when viewed as day-to-day progress. But when we step back and look at this past year, I’m overcome with the hope for what next year has in store.

I’d like to dedicate this blog post to some of Emelyn’s major accomplishments this past year:

Emelyn is officially a bona fide walking machine. There are several logical and not so logical things we’ve attributed to this major achievement:
  1. Physical therapy: At this point, Emelyn has likely had more than 250 PT sessions since she started PT at five months old through early intervention.
  2. ABA therapy: Emelyn’s ABA plan calls for three walking sessions per day at seven minutes per session. By my estimates, that’s nearly 13,000 minutes of practice just at her ABA clinic.
  3. Equipment, equipment, and more equipment: AFOs, SMOs, gait trainers, walkers, threatogs, etc.—we’ve had it all. Surprisingly, I believe it was a little pink helmet that I’ll attribute to being the best piece of equipment to move Emelyn to independent walking. It gave us all peace of mind and let her practice her walking skills on her terms.
  4. Medication: After reading about the cognitive improvements some other parents of children with DDX3X had reported after starting ADHD medicines, we spoke to every doctor we could about the possibility of trying similar medicines with Emelyn. Some were firmly a “no” stating that she had great attention for her developmental age, while others, like our pediatrician and developmental pediatrician, both thought it was worth trying. With the support of our developmental pediatrician, we started a very low dose of Focalin in July—Emelyn started walking just a few short weeks later. When she doesn’t have the medicine, she’s less stable and falls more frequently. Walking certainly wasn’t the outcome we were expecting, but we'll take it!

Standing up without any assistance
Another incredible motor skill Emelyn has gained recently is her ability to stand up from the floor completely unassisted. I remember the first time she used a stool to stand herself up about a year ago—I was amazed. And now, she needs no assistance what so ever.

When we started ABA therapy, our number one goal was functional communication. We didn’t care if it was verbal language or some other form, but we wanted to be able to communicate with Emelyn—to know her wants, desires, needs, etc. This year we definitely got that. Last November Emelyn began using some basic signs to help her express herself. We started with a highly motivating sign for Emelyn: read. Then we added other highly motivating signs: eat, graham cracker, cereal, sing, etc. Now, she’s using 30+ signs to communicate her needs. While she still has no spoken words, we now have a much better idea of what she needs and wants. Emelyn uses an iPad to communicate as well, but I’ll be honest and say she seems to prefer the sign language. Now we use sign language as a motivator with her. Her physical therapist will tell her, “I’ll teach you a new sign if you’ll walk around the floor.” Does your five-year-old know two languages--our five-year-old does!
Emelyn also got a fabulous new haircut this year!
We were able to donate 12 inches to hair we share.
Playing with her sisters
For many, walking was probably the most remarkable accomplishment of Emelyn's year, but for the four of us who share a household with Emelyn, it was something more subtle. Last month, Aubrey turned a cardboard box into “Aubrey’s CafĂ©” and asked me to order some food from her menu. I obliged and the next thing I knew, Emelyn followed suit. She stood at the little window and had a meaningful few moments with Aubrey as they passed plastic food back and forth to each other. Aubrey looked at me with astonishment and said, “Emelyn just played with me.” It was truly remarkable and it only took five and a half years in the making.
Emelyn placing her order at Aubrey's Cafe. 
Sunday school
Earlier this year we joined our church and each of us found a spot to plug in—except Emelyn. Our church doesn’t have a specific special needs ministry, but that wasn’t a must for us when joining a church. We just wanted a place where we all, including Emelyn, felt at home. If you could see Emelyn on Sunday morning, you would know she feels loved at our church. Everyone knows her and interacts with her and not a sole is irritated when she decides to get vocal during quiet moments or in the middle of the sermon. That being said, we were still wanting to get Emelyn into a Sunday school class, but we were concerned that Emelyn would need an aid or one of us with her—both for her safety and for the church’s liability. Back in the summer, I was asked to serve on a committee at church—I hadn’t originally signed up (Patrick gave me the you-can’t-possibly-volunteer-for-one-more-thing look) but got a call from our pastor requesting my participation. It was on that committee that I got to know the kindergarten Sunday school teacher, Sharon, who just happens to be a special education supervisor for one of the local public schools. After a committee meeting one Sunday she expressed her interest in having Emelyn join her Sunday school class. The next Sunday, Emelyn started in Ms. Sharon’s Sunday school class. Ms. Sharon is knowledgeable about ABA principles and sign language, which makes her a perfect match for Emelyn. We are excited to see what Emelyn’s experience will be like with typically developing children her own age—after all kindergarten is coming. God certainly knows what he’s doing, sometimes before we know what he’s doing.

Overall, 2018 was a remarkable year for Emelyn. Day-after-day, Emelyn made progress toward being more independent. And with each new skill she gains, she glows with pride and excitement. For us, day-after-day, our hope for Emelyn’s future grows. No longer do we grieve the child we once anticipated. We know now, Emelyn, just the way she is, was who we were meant to have.

We are grateful for your support this past year—this journey would not be filled with hope if you weren't here with us. Thank you! May 2019 bless you and your family with hope, love, and giggles.

Get a picture of all three girls for the Christmas card...

...it will be easy they said...
...they lied.

Monday, November 26, 2018

What we learned at the Philadelphia family conference

Last month our family traveled to Philadelphia to take part in the 4th annual DDX3X conference. As I’ve written in previous posts, these conferences have multiple purposes, but for the sake of brevity, I’ll only highlight the research updates as it relates DDX3X in this post.

Twelve world-renowned scientists traveled from around the country to participate in the conference. On the first day, the researchers participated in a roundtable discussion to share their progress and consider ways to collaborate. The following day they presented their findings to approximately 35 DDX3X families from the US and Canada. Their presentations showcased the incredible progress they have made as well as mapping out the road ahead. 

The chief researchers, the Sherr Lab at UCSF, led by Dr. Elliot Sherr, continue their work to understand the basic science behind how mutations of the DDX3X gene impact brain development and function. Their work with induced pluripotent stem cells has led to a greater understanding of the expression of the DDX3X gene and its function in the development of the brain. The Sherr Lab has also enrolled over 80 DDX3X individuals in their study examining the individual’s clinical presentation and how it correlates to that individual’s unique mutation. They are also working to develop a “knock-in” mouse to examine how missense mutations affect brain development in the mouse model.

Emelyn befriended Ruiji Jiang, a graduate student in Dr.
Sherr's lab, in hopes of having a few clicks on his laptop. 
The Sherr Lab recently collaborated with Dr. Debby Silver and members of the Silver Lab from Duke University in a study entitled Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development. This paper will be published next year. Dr. Silver also came to Philadelphia and discussed her lab’s multi-pronged approach to thinking about mechanisms of disease produced by the DDX3X mutation. In particular, her lab is interested in prenatal brain development and is using a mouse model to understand neural generation and proper neural migration. 

Mariah Hoye, a fellow and postdoctoral research associate
from Duke Institute for Brain Sciences, and Emelyn hit it off.
Mariah shared her experience at the conference in this article
The Seaver Center at Mount Sinai has identified DDX3X as one of its top research priorities and has a new lab, led by Dr. Silvia De Rubeis, which is dedicated to the study of DDX3X. The lab has developed a DDX3X mouse model and is currently undertaking research on the mice to better understand the impact of the mutation on social, cognitive, sensory, and brain tissue development. Additionally, Mount Sinai is also enrolling DDX3X patients in their clinical research program to better understand the clinical aspects of the gene mutation. Mount Sinai hopes to combine the findings of these studies to identify potential therapeutics that may be ultimately brought to clinical trial.
Dr. Maria Escolar, Director of the Program for the Study of Neurodevelopment in Rare Disorders at the University of Pittsburgh, continues to enroll families in her DDX3X natural history study. These detailed studies provide information on the course of the disorder as the children develop over time with the ultimate goal of creating a well-defined benchmark and an appropriately designed clinical trial once a therapeutic is identified. Currently, Dr. Escolar and her team have ten children enrolled in her study and continue to recruit new patients. 
Dr. Sanchita Bhatnagar from the Neuroscience Department at the University of Virginia, attended and detailed her previous work on X reactivation for Rett Syndrome. Dr. Bhatnagar is extending this research to look at ways in which to induce the unaffected DDX3X gene in the second X chromosome to express itself.
We were thrilled to meet Dr. Bhatnagar from UVA. We plan
 to visit her on our next trip to UVA with Emelyn.
The DDX3X Foundation, which has no paid staff, has reached a critical point where we have an extraordinarily teams of researchers focused on curing this condition, but more funding is needed to expand resources. Because of the leadership of parents, 100% of all money raised goes directly towards research.

Our family is grateful to this incredible team of researchers and the parent leadership of the DDX3X Foundation for making the 4th annual conference a reality. Assembling twelve world-renowned scientists in a room together, plus coordinating food, hotel, and activities for 35 special needs families is no easy feat, but a group of dedicated parents, led by Beth Buccini and Liz Berger, made it happen.

Our family is doing our part—we have enrolled Emelyn in multiple DDX3X studies; we travel to DDX3X conferences to meet other families and researchers (often giving up our own vacations); we write (ok, I write, Patrick proofreads) website copy, blog entries, and even a thesis about DDX3X; we share in successes and heartbreak with other families as we raise children with similar challenges to Emelyn; and we raise money to further research.

We invite you to join us in our efforts by making a tax-deductible donation to the DDX3X Foundation in honor of Emelyn at ddx3x.org.

Our family thanks you in advance for your consideration!

Sunday, November 11, 2018

Navigating the rough seas that come with advocating for your child

If you've ever sat through an IEP (individualized education plan) meeting, you've likely found yourself confused, determined, frustrated, curious, optimistic, pessimistic, and a hundred other competing emotions. And it's not just parents, I know educators who feel the same way in these meetings. None of our children, special needs or not, come with a road map. And when parents and educators sit down at the conference table for an IEP meeting, tensions about what's the best educational path are inevitable.

In 2015, when Emelyn was approaching three years old, we began the intake process for her IEP at our local school system. Despite my best research, I still felt unprepared, confused, and timid. Were we walking the correct path, with the correct people, with the correct goals? I had no idea, but January of 2016 came and we signed the IEP and sent Emelyn off to the local school system’s preschool special education program. 

Fast forward several months and it was clear our IEP was not a success. Emelyn was not making progress—if anything, we were seeing regression since her departure from early intervention. After several meetings we decided to pull her out of the school system and enroll her in an ABA-based clinic. (See my two other blog posts about our ABA experience: New diagnosis, new therapy, new opportunities and ABA, it may not be what you think it is.) 

ABA was an immediate success for Emelyn. Within weeks of starting she gained skills we thought were years in the making. And she began opening up to the world around her. I’m convinced, more than two years later, she would not be where she is at today without the wonderful people and solid plan at her ABA clinic. They love her and they push her to be the best Emmy she can be. But, her time at her phenomenal ABA clinic will come to an end in 2019. She will age out of their program and we will return to the school system to continue Emelyn’s educational journey. This time, though, I will be a different kind of advocate for Emelyn. I have experience and knowledge that I didn’t have last time.  

This time last year, as I approached my final essay for my master’s degree, I sat with my advisor, curious about how in the world I was going to find inspiration to fill approximately 50 pages with coherent and purposeful words. With a broad umbrella of leadership, my advisor asked me what I was curious about and what would be meaningful for me to research and write about. Without much hesitation I shared my frustrations with advocating for Emelyn in an educational setting—how I lacked confidence in the next best steps, how the relative newness of DDX3X meant there wasn’t much data, and how I wasn’t alone in these feelings. And an idea was born.

Before I could write a word, I needed data—there was a tremendous amount of informal data floating around our private DDX3X Facebook group, but I needed data suitable for a scholarly publication. Collecting data on human subjects requires involvement from the Institutional Review Board (IRB) and when you’re talking about a vulnerable population, they (understandably) make sure you follow all the rules. Their approval process took two months, an 18-page application, and a lengthy survey. Once I had the IRB seal of approval I started collecting data and researching relevant peer-reviewed journals. I probably could have researched the thing to the end of the internet, but luckily my advisor, the wise Abrina Schnurman Crook, Ph.D, reeled me in. At last, after months of writing, my final essay was off to the second reader and this is where I held my breath. The second reader and director of the MALS program at Hollins University is a well-respected, retired superintendent of schools, Lorraine Lange, Ed.D. Would she tear it apart or bless it?

To my pleasant surprise, my final essay received her blessing (with a few small changes, mainly to grammar because let's be honest, that's not my thing) and I had the last requirement for graduation complete. My master’s journey came to an end. I’m embarrassed to admit, that was more than eight months ago. From time to time I talk to different DDX3X parents and share the completed essay to help them on their educational journey, I just haven’t devoted the time to sit down and prepare a blog post dedicated to sharing it broadly. Shame on me. But, finally, without further delay, here it is:

You’ll find I grouped the essay by barriers—barriers our children face as a result of their DDX3X mutation, barriers our children face in the school system, and barriers parents face as they advocate for their child during the educational journey.

Is the essay perfect? Most definitely not, but it’s a start. If you’re a parent wondering aimlessly on the educational journey, I hope its content will provide guidance and direction to you. That is its intent—to help you navigate the rough seas that come with advocating for your child.

Graduation day with Patrick and Aubrey.
It was a gorgeous day on the Hollins campus.

Tuesday, May 15, 2018

Q & A about Emelyn’s natural history study experience in Pittsburgh

Two weeks ago, we headed to Children’s Hospital of Pittsburgh of UPMC (CHP) for a natural history study. It was a great trip and it’s taken me two weeks to pull out the important pieces into a Q & A for other parents considering a trip to Pittsburgh.

The Pittsburgh skyline from Mount Washington.
My goal of this post is to help you understand our experience and determine if taking part in the natural history study is right for your child and family.

Why does a natural history study matter?

First, you may be wondering, what is a natural history study? Until last fall I couldn’t answer that question. It was on our DDX3X trip to San Diego that two of Dr. Maria Escolar’s associates explained what a natural history study is and why it’s important.

Rare diseases, especially newly discovered disorders like DDX3X, are poorly understood. There are only a handful of patients in the world and each patient, typically, has a different doctor. With such a limited pool of patients and small number of treating doctors, knowledge about DDX3X is siloed. When many patients come to one doctor, like Dr. Escolar, and go through a series of evaluations, imaging, and exams, their journey adds to a collective body of knowledge. Dr. Escolar’s interest is to follow our affected children over time to collect health and development information to shine light on DDX3X.

On a micro level, natural history studies benefit the participating family. Dr. Escolar, who has seen approximately eight children with DDX3X as of our visit on April 30, 2018, can offer far more expertise than our Virginia-based pediatrician and developmental pediatrician. We are very pleased with the care our local pediatrician and developmental pediatrician offer us, but they’ve never treated another child with DDX3X (that they know of anyway), so their knowledge of DDX3X is narrow. Fortunately, their expertise in working day-in and day-out with children with special needs makes them highly skilled at helping us navigate our journey with Emelyn. However, they’re at a disadvantage due to the rare nature of DDX3X. For that reason, both our pediatrician and our developmental pediatrician urged us to participate in the natural history study with Dr. Escolar. And both are eager to see the final report from Dr. Escolar.

On a macro level, natural history studies advance collective knowledge and influence research. The collective data from all the participants can be used to gain insights on the progression of the disorder, evaluate currently available treatments, therapies, and pharmaceutical that offer benefits, and contribute to future development of potential treatments, therapies, and/or medication. Because there is no known treatment, therapy, and/or pharmaceutical to “cure” DDX3X, these natural history studies show outcomes in absence of intervention. That’s important should an intervention (such as gene therapy or a pharmaceutical) become available—the collective data from the natural history studies can serve as the control group. It’s the baseline to show the FDA the disease course for untreated patients. But more importantly, development of a “cure” requires a deep understanding of the rare disease which can only happen through studies such as natural history studies.

What is the basic flow of your time at CHP?

Each patient’s journey is a little different depending on when the MRI scanner is available and when different therapists are available. Below is our itinerary as an example only. Expect your itinerary to include the same basic experiences, but the order and timing will likely differ.

Day #1:
On Monday afternoon we met with Dr. Maria Escolar. Before our meeting, Emelyn spent the morning being evaluated by a team of folks. Emelyn really enjoyed all the therapists and Dr. Escolar. She was fully cooperative and full of giggles all day. They did a wonderful job of making Emelyn think she was part of a fun day where she was the center of attention. Each therapist was patient and engaging, plus they all used ASL (sign language) to communicate with Emelyn. You can tell Dr. Escolar and her team enjoy their work.

Behavioral audiology evaluation: This is basically a series of hearing tests that rely on a child’s behaviors versus spoken words. It took about 45 minutes.
Sarah was the clinical audiologist who examined Emelyn.
Physical therapy evaluation: This is a familiar evaluation for many of us. Emelyn climbed stairs, walked, stood up, stand down, etc. We brought a few books from home to help with positive reinforcement to encourage Emelyn to show off her skills.

Shannon conducted Emelyn’s PT evaluation.
Speech and cognitive evaluation: This session consisted of several tasks and questions to determine Emelyn’s speech and cognitive levels. While I don’t think these tests are perfect, I didn’t see anything that surprised me in her abilities or inabilities to complete the tasks or requests.

Allison and Emelyn “played” several games together.
Physical exam with Dr. Escolar: Throughout the morning and early afternoon we didn’t see Dr. Escolar, but she was clearly following up with each of the above folks to review their findings. After she examined (i.e. played with) Emelyn, we sat down and chatted for more than an hour. Not only was she fully informed of all the assessments Emelyn had just gone through, she had thoroughly reviewed Emelyn’s medical records and was prepared to answer the questions we had submitted on our paperwork. It was refreshing honestly. I can’t tell you how many doctors we’ve met with who clearly haven’t read the paperwork we’ve spend a significant amount of time completing.

Dr. Escolar examining Emelyn. There were lots of giggles.
Day #2:
On Tuesday morning Emelyn had an MRI under general anesthesia. We arrived at CHP at 7 am to be prepped for an 8 am scan. Once again everyone was great with Emelyn. While we were waiting for Emelyn, Deanna Steele, a genetic counselor who works with Dr. Escolar, came to speak with us. Her goal was to answer genetics-related questions we might have and complete a quick genetics questionnaire for the natural history study. 

Emelyn waiting for her MRI scan.
The MRI was the only part of our trip that didn’t go smoothly. Emelyn became very combative and her heart rate jumped up for about ten minutes as she was coming out of the anesthesia. After a hectic ten minutes, she dozed for about 20 more minutes and woke up without any trouble. We're blaming it on the red hair. We were on the road by 11 am to head back home.

What did you learn?

The feedback we received based on all the tests/assessments was similar to what we’ve heard from our local developmental pediatrician (just more in-depth), so that was good— it told us we’re on the right path. A summary of our visit was posted immediately on myCHP and we expect a full report in the next week or so. Here is a quick summary of Dr. Escolar’s insights and recommendations for Emelyn:
  • Emelyn's physical therapist should work on her protective reflexes. She's still exhibiting some of her infant reflexes which could be deterring her from walking.
  • Emelyn should utilize an augmentative device to better communicate. While she’s showing significant advances with using sign language, her fine motor skills are only at an 18-month level, whereas her receptive language is at least at a 24-month level. This leads Dr. Escolar to believe Emelyn may be frustrated that she can’t express everything she has to say using sign language because her fine motor skills are holding her back.
  • Because Emelyn uses movements to compensate for her low muscle tone and for sensory issues, Dr. Escolar doesn’t recommend the use of any medications to help with her movement disorder. (This was a question our development pediatrician at UVA posed.)
  • Emelyn's developmental age correlates with her attention span, therefore, Dr. Escolar did not recommend using any medications for attention deficit. (This was one of our questions...to medicate or not?)

We did ask what consistent barriers Dr. Escolar is seeing in our DDX3X children and not surprising her response was: language. Even girls who have language struggle with language. Some see a regression of their language skills whereas others, like Emelyn, are completely nonverbal. I'll be very interested to hear her present later this year in Philadelphia at the 4th annual DDX3X family conference after she's seen even more children.

Was the experience valuable?

Yes! We’ll likely go back next summer before Emelyn starts school. Dr. Escolar seems to have an interest in helping parents get their kiddos what they need from an educational standpoint and I anticipate needing her support with our local school system when the time comes. Her testing/assessments were very thorough—far more so than anything we’ve been through before. Bottom line, it was worth the trip.

How did we enroll Emelyn in the natural history study?

We contacted Mary Brannaman, Program Coordinator for Program for the Study of Neurodevelopment in Rare Disorders at Children’s Hospital of Pittsburgh of UPMC:
451 44th Street
Plaza Building, Fourth Floor
Suite 407
Pittsburgh, PA 15201-1138
P: 412-692-6350

Mary sent us several pages worth of paperwork to get the process started. Once the paperwork was returned, Mary worked with us on scheduling. Mary was super patient with me as I was very particular about scheduling Emelyn an early MRI appointment. She diligently worked her magic to orchestrate all the appointments into one and a half days. Once it was all finalized, we received an itinerary with all the details outlined. You’ll want to print this out and bring it with you.

What are the lodging options?

Mary helped us with lodging as well. She made our reservations at the Hilton Garden Inn/Pittsburgh University Place. For our two nights, we paid $299.92 ($114/night for the room, $20/night for parking, plus taxes and fees). Considering it was graduation weekend for University of Pittsburgh this rate was very reasonable, however, there may be other option. I honestly didn’t do my research. A couple things to note about this hotel based on our experience:
  • There is no pool. With girls who love water, I felt that was worth mentioning.
  • I didn’t find the shuttle to be worth the effort. It was well-worn and smelled like fuel, plus by the time you tip your driver each way, you might as well pay for parking (assuming you have a car). We also had to board the shuttle from the main level of the hotel which wasn’t easy to get to with a stroller/wheelchair. It required a wheelchair lift (or a Patrick to just carry Emelyn up and down the stairs in her stroller).

Mary also connected us with the Ronald McDonald House, however, we did not end up staying there. While we did fill out the necessary paperwork to be added to the waiting list (they do not have reservations like a hotel), I missed the call from them on the morning we were traveling to Pittsburgh. Once we got on the road I realized that I had missed the call and I called back. No one answered so I had to leave a message, but I never received a return call. I assume the call was to tell us we had a room, however, since they didn’t leave a message and I was unable to speak to anyone I’ll never know.

Staying at the Ronald McDonald House is an affordable and convenient option. NDRD is located in the Plaza Building which also houses the Ronald McDonald House (it’s really a hotel-like building, not a house), so you’re right there for your appointments with Dr. Escolar. From the Plaza Building, there is a breezeway that connects to the hospital for the MRI, hearing screening, and cafeteria. It’s certainly a worthwhile option to consider, just be vigilant about answering your phone the morning you head to Pittsburg and have a backup hotel reservation (which Mary can help you with).

What tips do you have?

Don’t rush yourself. Plan to travel the day before your appointment to allow for a full night of sleep the night before. While you can do everything in one day, I recommend scheduling the audiology appointment and all of Dr. Escolar's assessment on the first day and then the MRI for first thing the second day. Emelyn’s scan was at 8 am (7 am arrival at CHP) and we were on the road by 11 am to head back home.

Bring or purchase snacks for your time in the NDRD. It’s a long day. We started with audiology at 8:30 am and didn’t wrap up with Dr. Escolar until after 2 pm. There isn’t much waiting between each assessment, which is nice because it keeps things moving, but also didn’t allow for lunch. We were able to grab a snack between each session to keep from getting too hangry. (The cafeteria is close by and has lots of snack options, but don’t plan on being able to sneak off to the cafeteria, grab them before you get started.)  

Emelyn enjoying some grapes after seeing Dr. Escolar.
Children's Hospital of Pittsburgh is ranked one of America's best children's hospitals. If you need to see a specialists because you don't have access to one where you live or you want a second opinion, ask Mary for help scheduling an appointment while you're in Pittsburgh.

Sign up for myCHP so that you can access your child's health information online. It's very easy and convenient once you get back home.

Print Mary’s itinerary and bring it with you. It’s your roadmap for your time at NDRD/CHP.
Don’t worry with the hotel shuttle. Travel around Pittsburgh isn’t difficult and parking at CHP (via the Mid Campus Garage) is only $7.

If you want to stay at the Ronald McDonald House…answer your phone. They don’t leave messages and didn’t return my phone call.

Check out Pittsburgh while you're there. We rode The Duquesne Incline. It provided wonderful views of the city from atop Mount Washington. At $5 per person round trip, it's a bargain-priced experience.
Emelyn checking out the skyline of Pittsburgh from inside
the 100+ year old cable car on The Duquesne Incline.
If you have questions I don’t address above, please reach out to me at jamiesnead@outlook.com and I’ll gladly answer your questions. 

Saturday, May 5, 2018

I have a confession to make

Confession: This blog exists for many reasons and one of those reasons isn’t all that altruistic.

Here are the five reasons this blog exists:

Reason #1: I want to be a resource for families. When we received Emelyn’s diagnosis in September of 2015 there was only one medical journal about mutations in the DDX3X gene and their link to developmental delays and intellectual disabilities. There was no website, no foundation, no video, no brochure...nothing! This blog was my way of giving DDX3X a real spot on the world wide web for folks to learn about DDX3X.

Reason #2: Writing is a form of therapy for me. Each blog post allows me to unpack the latest Emelyn happenings, be it joyful or challenging, in a deeply reflective way. While writing does not possess this kind of therapeutic power for everyone, it certainly does for me.

Reason #3: Language matters. I’ve developed a love of language over the last few years and it’s important for me to put thought and intention into how I frame up Emelyn’s strengths and weaknesses. I never want to speak about Emelyn in a way that evokes pity or paints an unrealistic picture. This is especially important for families who just received their child’s diagnosis. I want them to leave my blog with hope for their daughter.

Reason #4: Emelyn has a fan club made up of family, friends, church members, co-workers, friends of friends, doctors, therapists, researchers, teachers, and even perfect strangers. These are the people who love and pray for Emelyn, donate money to the DDX3X Foundation in honor of Emelyn, fight insurance companies and school systems on behalf of Emelyn, and cheer for Emelyn at each and every accomplishment. Because of the love from these folks, it’s important to me that I keep folks informed of  how Emelyn’s doing.

Reason #5: Lastly, and here is where the confession comes in, this whole blog thing was a course requirement. Yes, that’s right, I had to do it! In early September of 2015, as I sat in my fourth course for my masters degree, I was informed by Dr. Ken Nicely that one of the course requirements was to start a blog. Seriously! What the heck was I going to start a blog on? Couldn’t I just write a paper or take a test. Then, as divine destiny would have it, just a few days later came the call from our genetics counselor with Emelyn's DDX3X diagnosis. It was that sequence of events that led to this blog.

While that course ended in December of 2015, the blog has lived on. No longer is this blog a four-credit course requirement for graduation—instead it’s a labor of love to share Emelyn’s story with you and to raise awareness about DDX3X.

It’s not always easy to keep current on the blog—for me as the writer and for you as the reader. We live busy lives. Some days I grow weary of writing. Between work, school, and volunteer work I have far more screen time that I’d like, but today I had confirmation that this blog matters. A mom from Australia was doing what every mom does when you have an undiagnosed child and desperately needs answers—she turned to the internet. This particular mom found this blog and saw her daughter in the words and photos of Emelyn. She visited DDX3X.org to further her research. With her momma-gut guiding her, she consulted her daughter’s doctor and requested they look for a change in her daughter's DDX3X gene. Turns out, her momma-guy was right. Her daughter has a mutation in her DDX3X gene. Not only did this blog get me an A back in 2015, it got a family answers and direction.

So here is where I’m going to get a little sappy in you. Do you ever feel like God has a plan for you? I certainly do. He knew good and well that I wasn’t going to start a blog on my own—He (through Dr. Nicely at Hollins University) had to make it a course requirement to get me started. And because of that course requirement I’m helping others get answers to the questions they have about their child.

So, there you have it, I’ve confessed my intentions and I have to say, I’m proud of this little venture. And I’m proud of you, my faithful readers, for sticking with me. Your support means so much to our family.

(I leave you with the following video of Emelyn sporting her new helmet and walking like a champ.)

Thursday, November 23, 2017

What we learned at the San Diego family conference

On November 2, Patrick, Aubrey, Emelyn and I boarded a plane to San Diego where we spent four days with nearly 30 other DDX3X families. There are two reasons we make the trip to these family weekends. First, we have the chance to spend time with families who get what it’s like to have a daughter with DDX3X. They understand the struggles and the joys. We learn from them and they learn from us. We share a powerful connection and it’s important to nurture that bond. Secondly, we get to hear from medical professionals who are actively researching the DDX3X mutations. At the bottom of this post, I’m including bios for the medical professionals who were in attendance at our San Diego family day.

Sisters enjoying the world at 25,000 feet.
The first three days were filled with fun family activities…Sea World, music therapy, swimming, and more. 

The final day was the family conference. (Check out this article from the San Diego Tribune about our DDX3X family day.) It was packed with so much great information from the medical team that it’s taken me nearly two weeks to distill it all down into the following key points:

DDX3X Foundation dollars are already advancing our understanding of the DDX3X gene…

Pediatric Neurologist Elliott Sherr, MD, PhD at the University of California, San Francisco is heading up research to better understand the function of the DDX3X gene—what does it do in its normal, non-mutated form and what happens to its function when it mutates? The funds raised are paying for the scientists who are exclusively studying DDX3X at Dr. Sherr’s lab. Additionally, the funds have enabled the creation of a mouse model. (And if you’re a science geek, then you’ll be excited to know that CRISPR technology was used to create the mouse model.)

Dr. Sherr and his research team have already made a number of significant advances in the short time they have been working on DDX3X. Nearly 70 children, including Emelyn, have enrolled in a study where we shared MRI scans, genetic information, saliva samples, and developmental data. From that information, Dr. Sherr and his team have tabulated the data and made several observations so far:

MRI scans show a small/thin corpus callosum (this is the band of nerve fibers joining the two sides of the brain), a smaller cingulum bundle (this is the nerve cell highway), and, in about a quarter of the girls, abnormally folded brain tissue known as polymicrogyria or PMG.

Emelyn does not have PMG but does have a “diffusely thin corpus callosum,” as well as a “small and deficient dorsal cingulum bundle” (dorsal means back) and “missing ventral cingulum bundle” (ventral means front). She also has a small, underdeveloped hippocampus.

The type and location of the mutation on the DDX3X gene appear to correlate to the individual’s level of function. There are four types of mutations that can happen: missense, nonsense, frameshift, and splicing. These mutation types can happen at various places on the DDX3X gene. It appears that about 90% of mutations happen inside the helicase, which is on the last two-thirds of the gene.

Emelyn’s mutation is a frameshift mutation occurring at Isoleucine 214, changing what should have been an amino acid to a threonine residue, creating a premature stop codon at position 7 of the new reading frame, i.e. p. Ile214ThrfsX7. What does all that mean? It means this “spelling error” causes a loss of normal protein function. From what I can tell (keep in mind my last biology class was in tenth grade), Emelyn’s mutation, at Isoleucine 214, happens about a third of the way into the sequence causing the protein to be more altered than someone with a mutation further down the sequence.

Why, oh why, didn't I pay better attention in high school biology.
Additionally, Dr. Sherr and his team are studying both normal DDX3X genes and mutated DDX3X genes in a test tube model in order to better understand how a normal DDX3X protein functions. So far they have learned that a normal DDX3X gene unwinds quickly, whereas a mutated DDX3X gene unwinds at a slower pace. In other words, the mutated DDX3X gene does not function at 100% like a normal DDX3X gene. When the time comes, the model used to study function can be adapted to use drug screening technology to test hundreds or even thousands of candidate drugs in a single day.

Dr. Sherr is confident that his team can dramatically accelerate their efforts, continue to make significant advances, and move closer to a viable treatment for girls with DDX3X. However, in order to keep him and his team going, we have to keep funding coming.

The next step is to create stem cell lines to better understand how normal DDX3X functions to maintain cell health. Then, develop an understanding of how specific mutations in DDX3X affect how that cell functions. Emelyn and I had blood drawn in California for this process, as did a few other mother/daughter pairs. Stem cell lines will be made from our blood to advance understanding of both normal DDX3X and mutated DDX3X.

Additionally, a mouse model is already in the initial stages as mentioned above. The model will be genetically engineered to address two key biological questions:
  • Can the mouse model (with the same mutations as our girls) show similar physiological and cognitive challenges as girls with a DDX3X mutation?
  • If a mouse is born with a DDX3X mutation, can the team genetically engineer the mouse after birth to a mouse without a DDX3X mutation? This will help the team understand whether fixing the biology of DDX3X after birth can lead to a better or even normal developmental outcome.
Not only are our DDX3X girls rare, so are DDX3X parents…

The DDX3X Foundation was created in 2016 by two DDX3X moms, Beth and Liz. They are working moms who have taken on the role of co-presidents of the DDX3X Foundation as a volunteer gig. Beth’s daughter was the first person diagnosed with DDX3X. She is our connection to Karlla (see below). Liz’s daughter was also diagnosed shortly after the discovery of DDX3X. She is our connection to Dr. Sherr. These two moms, plus a team of other moms and dads (including our family), are fully vested in raising awareness for DDX3X and continuing to fund the research being led by Dr. Sherr’s team.

DDX3X moms and dads united with researchers to help
our gives live the richest lives possible.
Over the past year, our DDX3X family group has fundraised to provide Dr. Sherr and his team approximately $115,000. We need an additional $60,000 before December 31, 2017, to keep devoted scientists working on DDX3X. In 2018, we’ll need another $120,000. Dr. Sherr and his team are working to publish a peer-reviewed paper detailing what he and his team have learned about DDX3X so far. The hope is that the paper, which is about a year from publication, will garner attention from the National Institute of Health (NIH) to help accelerate our funding stream because advancing this to the level of a viable treatment will require $1 to $2 million dollars a year in the very near future. Until then, it’s up to the DDX3X parents to reach out to our networks to raise the funds.

You can help us get there…

Will you consider a donation to the DDX3X Foundation to advance research? You won’t just be helping Emelyn, you’ll be helping the approximately 160 diagnosed girls, plus the nearly 15,000 estimated undiagnosed girls who likely have DDX3X. And cracking the code on DDX3X will open doors to treating other rare diseases as well. The impact of this research is far-reaching. Contributions are coordinated through the Delaware Community Foundation and are tax-deductible. You can make a donation online at delcf.org/donations/ddx3x or you can mail a check, made payable to the Delaware Community Foundation, to PO Box 1636, Wilmington, DE 19899 (don't forget to put DDX3X Fund in the memo line).

Dr. Sherr was humble in his gratitude for our support,
both financially and through our participation in the ongoing
DDX3X study.
Thank you for your support along our journey…

I’m grateful you just spent the last 15 minutes reading this mammoth post that likely taxed your brain. But more than that, I’m grateful you love and care for our sweet Emelyn. It means more than you will ever know to have you on our journey.

I can't explain it, but every time I fly I crave Chinese food.
Immediately after the conference we headed to the airport
and had Chinese, of course. When I opened Emelyn's
fortune cookie it was empty. I'm still philosophizing about
the meaning of her empty cookie, but it gave me tingles
about her future.

Dr. Sherr and his team:
Elliott Sherr, MD, PhD is a professor in neurology and pediatrics at the Institute of Human Genetics and the Weill Institute of Neurosciences at the University of California, San Francisco (UCSF). He co-directs the Comprehensive Center for Brain Development at UCSF. In this capacity, he cares for children with neurodevelopmental disorders, including autism, intellectual disability, and epilepsy. In addition, he directs the Brain Development Research Program, a group that studies the genetics and biology of autism, and other disorders of neurodevelopment. The lab uses gene discovery to understand how disruption in brain development may lead to cognitive and behavioral impairments and they leverage these models as a basis for developing novel therapeutics. Dr. Sherr’s specific areas of interest include the development of proteomic biomarkers to enable early detection and treatment for autism, and the study of a newly recognized common cause of developmental delay in girls, the gene DDX3X. His lab has directed a large multisite brain imaging study that is helping to connect changes in brain structure and function to the clinical deficits observed in autism (Simons VIP). Dr. Sherr is also a member of a large epilepsy genetics consortium (Epi4k), for which he led a team that advanced our understanding of the genetic causes of severe childhood epilepsies. For his research, Dr. Sherr was the 2006 recipient of the Philip R. Dodge Young Investigator Award from the Child Neurology Society.

Dr. Sherr is a native of California and completed his undergraduate degree in philosophy and biology at Stanford University. He obtained his M.D. and Ph.D. at Columbia University in New York and completed his clinical training in pediatrics and neurology at UCSF. He lives in San Francisco with his wife, a biotechnology finance executive, and their three children.

On this particular trip our family had the opportunity to sit down with Dr. Sherr as well. He met with nearly every family there on Saturday one at a time. We were his first appointment at 9 am and ten hours later he was still meeting with families. Beyond the MD and the PhD, I have to tell you, he is an incredibly kind and personable man. He clearly cares deeply about each and every one of our girls. We were thrilled to meet with him and ask him some of our specific “Emelyn” questions

Thanks to our funding, Dr. Sherr has the following wicked smart individuals working with him on the DDX3X mutation:

Bethany Johnson-Kerner, MD, PhD is an Alpha Omega Alpha honors graduate from the College of Physicians and Surgeons of Columbia University, where she also completed her Ph.D. in neuroscience. She is currently completing her clinical training in pediatrics and neurology at UCSF. For her Ph.D. thesis project at Columbia, she generated induced pluripotent stem cells (IPS cells) from patients who had a disorder of peripheral nerves that control muscle function, called giant axonal neuropathy. She used advanced laboratory techniques to make those stem cells into nerve cells, studying both healthy cells and cells from patients. She also showed that she could restore normal function to patient-derived nerve cells by putting back the normal gene.
Dr. Johnson-Kerner will be creating stem cell lines to better understand how normal DDX3X functions to maintain cell health, then she will study how specific mutations in DDX3X affect how that cell functions.

Ruiji Jiang, MD, PhD is a dual doctoral student (physician-scientist) completing his thesis work in Dr. Sherr’s lab. Dr. Jiang will be working with Dr. Li to develop a method to screen for drugs that could repair the function of DDX3X in cultured cells.

Lindsey Suit, a Berkeley undergraduate, will be completing her honors thesis on the spectrum of clinical challenges faced by girls with mutations in DDX3X.

Brieana Fregeau is the research coordinator for the Department of Neurology at UCSF and Brain Development Research Program. I don’t have a full bio on Brieana, but I get the feeling she’s the grease that keeps this super smart team running smoothly.

There is an extra special, and also wicked smart, member of our DDX3X tribe who is vested in each and every one of our girls:

Karlla W. Brigatti, MS LCGC joined the Clinic for Special Children as its first genetic counselor in 2014, bringing extensive experience in clinical genetics and research from across the lifespan. She earned her Bachelor of Science in Cell and Molecular Biology from the University of Pittsburgh in 1994 magna cum laude and her Master of Science in Human Genetics from Sarah Lawrence College in 1998. Prior to joining the Clinic for Special Children, she was the senior coordinator of the FASTER Trial at Columbia University, the largest NIH-funded trial in Obstetrics and Gynecology to date, and later the founding coordinator for the Center for Prenatal Pediatrics at Columbia University, introducing multidisciplinary and state-of-the-art innovation to the care of highly complex pregnancies before and after delivery. After moving to the Lancaster area in 2006, she served as senior genetic counselor in clinical genetics, pediatric oncology, and neurology at the Children’s Hospital of Philadelphia (CHOP), working with families from across the globe for over five years in the Friedreich Ataxia Center of Excellence at CHOP on various natural history and clinical drug trials for the condition. She has authored over 20 lay and scientific publications, mentored undergraduate, graduate, and medical students, and served on the Human Genetics Faculty at Sarah Lawrence College. She is currently completing a one-year program in Rare Disease Clinical Research Training through the National Institutes of Health. In addition, she currently serves on the Board of the CROWN Foundation, promoting research in women’s and newborn health. Her research interests include gene discovery, implementation of personalized medicine, and rare disease advocacy. She is certified by the American Board of Medical Genetics and is a member of the National Society of Genetic Counselors. Karlla feels this experience has enriched and prepared her for her work at the Clinic for Special Children. She promotes the partnership between clinical care and innovative research to improve the lives of those with genetic conditions. That trust and mutual investment with the community is a key element to the Clinic’s longtime success in advancing Genomic Medicine. (I might add, this also makes Karlla an incredibly valuable member of our DDX3X tribe!)

In order to be, as Karlla put it, “clinical trial ready” Nicholas Bascou and Deanna Steele from the Program for the Study of Neurodevelopment in Rare Disorders (NDRD) at Children’s Hospital of Pittsburgh of UPMC were also in attendance on behalf of Dr. Escolar:

Maria Escolar, MD, MS is a graduate of the Escuela Colombiana de Medicina. She has a Master of Science in Human Nutrition from Columbia University and completed a residency in general pediatrics and fellowship in child development and behavior at Cornell University Medical Center in 1995. Dr. Escolar is board-certified in neurodevelopmental disabilities. She has 15 years of experience as a practicing clinician and researcher. Dr. Escolar has authored multiple original manuscripts, including two New England Journal of Medicine articles. She is nationally and internationally known for her work in neurodevelopment of children with leukodystrophies and mucopolysaccharidosis. Her research focuses on behavioral and neuroimaging outcome measurements.

NDRD was established in 2002 because of the need of help children and their families understand the overall impact of rare neurological diseases on child development. Our family is considering traveling to Children’s Hospital of Pittsburgh of UPMC to take part in a natural history study, but that’s a whole other blog post, so stay tuned.

There are other important members of the DDX3X medical team as well, but these are the folks we had the opportunity to hear from in San Diego.