Yellow Brick Road Project Q1 2021 HNRNPH2 Quarterly Newsletter
We would like to introduce you to our daughter Isla who is 3.5 years old and is the most delightful, joyful soul who we just adore. Isla was born in September 2017 weighing just 2.3kg. She was a very small, quiet and an easy baby. Isla was born with Microcephaly (Small head circumference) and Metatarsus Adductus (curved in feet) which saw her having casting on her legs from 6-10 weeks old (with weekly cast changes).
Nothing ever phased her, she never cried or got upset, even when the physio used the loud saw to cut her casts off each week. In fact, she almost fell asleep during one of these sessions. Isla was just the most content baby, so we were not really alarmed by the age of 6 months that she had not progressed much as it was just her nature to be quite “chilled”. It was not until she reached 12 months that her pediatrician noticed she was not hitting all the average milestones and referred us to see a Neurologist, Genetics team, Physio, Speech Pathologist and get her hearing and sight checked too. They were leaving no stone unturned. By this stage, it was obvious that she had Global Development Delay and hypotonia.
Like many of the other families, Isla spent her first two years of life being scanned, x-rayed, poked, prodded and breaking down every time we were across the desk from a doctor. We hated her having to go through all the tests but we knew it was something we had to do. The unknown was the worst part of the process, not knowing which path we were on and searching for the right direction. We were contacted by Isla’s Neurologist to grant permission for Isla’s blood to be sent for Whole Exome Sequencing investigation in case something was missed. We ended up forgetting about it because it had been months, so we presumed nothing was found. Then out of the blue, we got the call to come in. We knew something was found, so we were really nervous and curious.
Isla was diagnosed at the end of July 2020 by her Neurologist with the HNRNPH2 genetic mutation. At first we were shocked and upset, but shortly after we were relieved to finally have a path and journey. Our Neurologist handed us information straight from The Yellow Brick Road website as she had been doing her research prior to our meeting.
Today Isla struggles with her mobility because of her severe hypotonia. At the moment is only able to do a “bunny hop” crawl around the place. She is standing unassisted with an aid and is learning to use a walker to mobilize. Isla does not talk or say any words. Her communication is by way of shushing noises, grunts, croaking, hissing, laughing or blowing. Isla bounces up and down a lot, especially to music and constant stimming with her fingers/hands.
Through it all Isla has the biggest smile on her face and is such a delight to be around. She loves music and songs, cannot get enough of The Wiggles, Sesame Street and Trolls. Isla uses her own language and movement to express herself and is so affectionate. She will watch the same thing over and over again and still loves it every time. She is obsessed with the same toys (ones which play music) and presses the buttons over and over again. Isla’s biggest strength would be her social skills. She always looks at us and smiles, making great eye contact or wanting a reaction to the song that is playing. Isla is also big sister to two little brothers born in February 2020, Elliott & Harrison. Sometimes they take her toys and she will “bunny hop” after them and claim them back. You go girl!
With the help of intensive physio, speech therapy and now an international group of support, we hope Isla’s skills improve in time. No rush, she is perfect the way she is.
There are several different types of scoliosis, but the one most common among HNRNPH2 patients is neuromuscular scoliosis. This is an irregular spinal curvature where nerves and muscles are unable to maintain the appropriate balance and alignment of the spine and trunk.
Many HNRNPH2 patients have a condition called hypotonia, with low muscle tone throughout their bodies. Without full support from the muscles in the back, the spine can develop an abnormal curve as it grows.
Compared with some other types of scoliosis, neuromuscular scoliosis is more likely to be progressive and continue progressing into adulthood. This is generally more severe among patients who are not able to walk.
Neuromuscular scoliosis often appears early in a child’s life. Symptoms may include:
- leaning or uneven seating posture
- using arms for seating support
- uneven shoulder heights
- head off center from the rest of the body
- uneven hips or buttocks
- uneven shoulder blades
- arms hanging unevenly
X-ray images taken from the side and front are the main tool for confirming neuromuscular scoliosis and the severity of the curve. Other tests may also be used, including MRI, CT or CAT scan, bone scans or ultrasound.
There are non-operative treatment options, including bracing for smaller curves, physical therapy and wheelchair modifications. Bracing can prevent the curvature from worsening, but it will not correct it.
There are also operative treatment options such as spinal fusion surgery. The type of treatment suggested will depend on the patient’s age, the severity of the curve and the speed of progression.If you have any concerns about or suspect scoliosis for your child, please consult with your doctor.
Rare Disease 2021 was celebrated on February 28, and our Rare Disease Day fundraising efforts raised just over $10,000 towards our ongoing research project with Andlit Therapeutics!
Leading up to the big day, the Yellow Brick Road Project put together a range of videos to celebrate the uniqueness of our patients and to spread awareness of HNRNPH2 mutations and the current research that is taking place.
NORD Show Your Stripes
First up was our entry for the NORD Show Your Stripes Rare Disease Day video contest. This amazing video showcased the highs and lows of life with an HNRNPH2 mutation, and we were named joint grand prize winner of the contest!
We continued this Show Your Stripes campaign with several more videos highlighting more of our amazing patients and the determination and dedication they display every single day.
The Show Your Stripes video, along with the individual videos, can be seen on the YBRP Facebook page or on our YouTube channel for anyone not on Facebook.
Several of our international delegate families also made t-shirts with the amazing zebra logo created by board member Paula Tyson and wore these to help raise awareness on the day as well. Keep an eye on the website for more products featuring this beautiful logo, coming soon!
HNRNPH2 Animated Explainer Video
On Rare Disease Day 2021, we also released our first-ever animated video explaining HNRNPH2 mutations and our hopes for treatment to a wider audience. This video was gifted to the YBRP by HNRNPH2 grandmother Esther Ollech, with our very deep gratitude. It is available with subtitles in eight different languages to help to share this very important information with all of our international families.
This video can also be seen on the YBRP Facebook page or on our YouTube channel for anyone not on Facebook.
YBRP Committees Behind the Scenes
Along with the Board of Directors, there are currently two committees that support the work of the Yellow Brick Road Project. All committee members are volunteers and family members of HNRNPH2 patients.
Additional committees are being considered to assist in fundraising and grant applications. If you have any interest in joining these or either of the existing committees, please get in touch!
The Outreach and Action Committee (OAC)
Chair: Angela Lindig
Volunteers: Trish Flanagan, Paula Tyson, Lourdes & Gabriel Torres, Lynn Elko, Amy Lerner
This Committee, made up of all parents to children with HNRNPH2 dx, focuses on providing broad education and awareness of genetic conditions, genetic education, and awareness of resources available locally, regionally, nationally and internationally. The YBRP knows that so many children and adults go misdiagnosed or undiagnosed and we want to help end that diagnostic odyssey. The OAC aims to find more of the H2 tribe, but also seeks to help all families learn the root cause for the difficulties their loved one encounters. The value in a diagnosis, at whatever age, cannot be quantified!
The creation of an outreach plan to target specific audiences to help raise awareness and provide pertinent information is underway by the OAC!International Delegate Committee
International Delegate Committee
Our international delegates are working to improving lives of HNRNPH2 patients around the world. They attend conferences in their area representing the YBRP on an international stage, raise awareness of HNRNPH2 within their local areas, and act as a point of contact for local families across 20 countries.
The delegates are all parents or grandparents of HNRNPH2 patients and they meet once a month, representing the following areas:
United States: Trish Flanagan, Paula Tyson and Nicole Glenn
Canada: Andrea Blake
UK: Stacy Paddon
Europe: Andreia Zanelato, Andreia Ramos, Beatriz Cortés, Vera Makarova
Israel & Asia: Esther Ollech
Australia: Alana Fahey
The YBRP is pleased to sit on the Board of Directors of COMBINEDBrain—The Consortium for Outcome Measures and Biomarkers for Neurodevelopmental Disorders.
This organization, comprised of organizational parent-leaders, is devoted to speeding the path to clinical treatments for people with severe rare genetic non-verbal neurodevelopmental disorders for pooling efforts, studies and data. Currently, the COMBINEDBrain is focused on:
- Design and coordination of natural history studies and outcome measures
- Design and coordination of rodent model phenotyping and biomarker development
- Leveraging resources to fast-track preclinical readiness
We know that by working with other rare disease groups, we will get to our final destination of a treatment and cure for our children faster.
Executive Director Terri Jo Bichell worked as a documentary filmmaker, then became a public health nurse midwife after filming a difficult birth in West Africa. When her son, Lou, was diagnosed with Angelman syndrome at age 1, she switched to research, earning a PhD in neuroscience from Vanderbilt University in a quest to find treatments for Lou, who is now an adult. She directed the Angelman Biomarkers and Outcome Measures Alliance from 2016-2018 and now leads COMBINEDBrain, assisting other rare genetic neurodevelopmental disorders in clinical trial readiness.
Natural History Study Update
The newsletter will contain a regular update from the research team conducting the HNRNPH2 Natural History Study. Dr Jennifer Bain is the principal investigator and Olivia Thornburg is her Research Assistant. They are based at Columbia University in New York City, USA.
What is a natural history study?
A natural history study follows a group of people over time who have a specific medical condition or disease. The study collects health information in order to understand how the condition develops and how to treat it. It can be used as a baseline to determine if proposed treatments are effective.
As of 2021, we have enrolled a total of 53 individuals with variants in hnRNP H2, although many more individuals have been identified. The majority of individuals affected are girls, although we have confirmed variants in 5 boys. Our research has employed the use of a prospective testing battery where we administer assessments remotely to test for various neurologic, behavioral, psychiatric, developmental, and social factors in this genetic group. We have also gathered information from former genetic reports and medical records.
Our virtual family meeting in 2020 was a great success, thanks to you and yours. The meeting testing measures revealed similar clinical symptoms to that of the original cohort, including atypical facial features, neurologic abnormalities, atypical gait, and abnormal muscle tone, among other clinical findings. We encourage families to join us in this year’s 2021 family meeting. We are in the exciting planning stages and hope you will participate.
Our research manuscript was also recently accepted to the journal of Neurology Genetics, and is publicly available here: https://pubmed.ncbi.nlm.nih.gov/33728377/
We absolutely could not perform any of this work without you, and we are grateful to have disseminated our findings with the medical community. Our hope is that we will learn more about the natural history of hnRNP H2, including neurological predictors for prognosis in these children, and in turn teach future physicians about their etiologies. In doing so, we believe we can potentially improve the lives of those affected by our genes of focus.
- Paula Tyson