Our superhero son's diagnostic odyssey
Our beloved son, Leo, will turn ten this month. He is a happy child and always has a big smile for everyone. No wonder he is pretty popular among the kids in the neighborhood and his schoolmates!
His mom and I are always in awe of Leo’s determination and how he faces every adversity with a smile. He’s always been our superhero! Leo cannot walk, talk or even eat on his own, even though he was able to do all of that just a few years back.
Leo was a healthy baby who met all of his developmental milestones. He started walking when he turned one. Very soon after, he was running around and babbling words like other toddlers. Life was chugging along splendidly until he was about two and half years old. All of a sudden, we noticed he became increasingly unsteady and would fall after just a few steps.
At first, we thought he was going through a temporary clumsy phase. However, after a few months of watching his motor skills decline steadily, we began to get worried. We consulted a slew of specialists - neurologists, orthopedic doctors and ENT specialists to find what was wrong with him. He was put through a gamut of tests, all of which came back negative. We were at our wit’s end.
Leo’s motor and verbal skills deteriorated rapidly. By the time he was in preschool, he was in a wheelchair and his speech was slurred. He worked very hard with his gait-trainer to strengthen his muscles so he could stand and walk again. We now know there was nothing any of us could’ve done about it. He has a progressing degenerative disorder caused by a mutation in a gene that scientists are just beginning to understand.
Around 5 years of age, he also started having trouble swallowing his food. By the time he was six, he was only able to eat very soft foods. It was gut wrenching for us to watch Leo struggle to eat his favorite foods. Leo had always loved food, especially Japanese cuisine. My wife would take great pains to cook special pureed food for Leo that was healthy, tasty and nutritious. Each day, she spent hours preparing and feeding him a small bowl of pureed food. Meal times became increasingly difficult and were a huge source of stress for Leo and my wife, and would often leave them both in tears.
As his feeding issues continued, Leo started to lose weight and would often catch infections. Last year, we finally decided to have a gastrostomy tube (G-tube) inserted. It was a difficult decision, but now we feel relieved since he’s getting the nutrition he needs and the school nurse or aide can also feed him.
Over the years, we received many possible diagnoses for Leo’s condition from cerebral palsy to cerebral folate deficiency, all of which turned out to be wrong. We even took Leo to Japan to get some tests done. He had three genetic tests, all of which came back negative. Finally, in January 2017, we performed the whole exome sequencing test again and found that he had a variant form of IRF2BPL gene. But this diagnosis did not mean much to the physicians or us since nobody knew what this gene did.
Once we had this diagnosis, I would constantly scour the internet for the latest advances on this particular gene. Usually, I ended up with nothing but I continued to search every day. Our lucky break came in May of this year. I was browsing bioRxiv, an online pre-print server, where I stumbled upon a study by Drs. Hugo Bellen, Shinya Yamamoto and Michael Wangler, scientists at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital and Baylor College of Medicine. After years of trying to make sense of Leo’s condition, my wife and I were elated and excited at the prospect of finally learning something about this gene’s function.
I immediately reached out Dr. Yamamoto who invited us to attend a scientific meeting of the Undiagnosed Diseases Network (UDN), a national federal initiative to identify genetic causes of rare and undiagnosed diseases. This invitation turned out to be a life-changing experience for our family. Not only did we get to meet the NRI researchers and learn more about this gene, but were invited to participate in UDN discussions and present our perspectives as parents and primary caregivers. More importantly, UDN helped us get connected with other similarly affected families.
My family and I are forever indebted to these researchers for taking the time to patiently explain to us their findings on IRF2BPL mutation and how it was affecting Leo’s brain. They were even kind enough to invite our family to visit their laboratories in Houston. They showed us fruit flies with reduced IRF2BPL activity and comparable decline in motor abilities - compelling and powerful evidence that a change in IRF2BPL is likely the cause of Leo’s symptoms. During that visit, we were also fortunate to meet Dr. Huda Zoghbi, the world-renowned neurobiologist and director of NRI, who infused us with optimism for Leo’s future. We feel lucky to have the support of such dedicated researchers who are working hard to find a treatment for this devastating condition.
For several years, my wife and I had been desperately searching for answers about Leo’s rapidly regressing condition. Every single day, we watched him able to do less than before, which made us feel helpless and guilty. We couldn’t do much to help him, other than to make sure he was not in pain or under stress. Thanks to the efforts of this amazing team of physicians and scientists, we finally have some understanding of what causes his symptoms and can now focus our efforts towards finding a cure.
We are at the cusp of yet another long journey to find treatment for Leo and other children like him who have IRF2BPL variants. The huge difference this time around is that we’re not alone in this odyssey. We feel blessed to have the support of other families and talented teams of physicians and scientists who are as passionate as we are to find a treatment for this disorder. We, and a few other affected families, have formed a support group to raise funds for research.
For many years, I have chronicled Leo’s diagnostic odyssey on my personal website, “His Beautiful Smiles. After meeting with NRI researchers, I realized how valuable these records are for the researchers to solve a medical mystery. Now I am creating an online registry of IRF2BPL patients with the hope of helping researchers find a treatment sooner.
If Leo can run, talk and play with his friends, as he used to, it would truly be a miracle, a dream come true for our family! Finding a cure for this condition is our ultimate goal but we know this is a rather difficult undertaking that could take several years to accomplish. At this point, any improvement in Leo’s symptoms or halt in his regression will be a blessing for us.
