Laura and Thad Avery formed the FBXO31 Foundation in 2023 after 20 years of caring for their daughter, Kate, who had been diagnosed with cerebral palsy as a young child. In 2018, after genetic testing as part of a research study, they discovered that Kate had a de novo mutation in the FBXO31 gene which was causing her neuromotor disorder. Connecting with other families who are also affected has inspired them to create the Foundation to build a new community to blaze a trail, support research and find a cure for this ultra-rare disease.
”Do not go where the path may lead, go instead where there is no path and leave a trail.
Ralph Waldo Emerson
About FBXO31
FBXO31- related cerebral palsy (CP) is a neurodevelopmental disorder caused by a mutation in the FBXO31 gene – which has only recently been linked to cerebral palsy.1,2 The patients identified to date carry the same variant in FBXO31 (p. Asp334Asn). The FBXO31 variant can be a de novo (new) mutation that occurs at the time of conception, or it may be inherited from a parent. Research is currently underway to determine how changes in the FBXO31 gene impact the function of the neurons in the brain, neurological development and functioning. Understanding more about the gene’s function will help us move towards finding much needed treatments for this ultra-rare condition.
Most individuals have additional barriers to overcome in order to learn the basic skills like sitting, walking, speaking and feeding themselves. The condition is generally thought to remain constant through life, not worsening, but presenting different challenges as individuals grow and mature. There is much to learn about the disorder, and we hope to identify additional patients, clinicians and researchers who are interested in supporting research and working together to identify treatments.
Features of FBXO31 related Cerebral Palsy may include:
- Hypotonia (low muscle tone)
- Developmental delay
- Speech delay
- Intellectual disability
- Ataxia
- Movement disorder
- Seizures
- Strabismus
- Autism
Not all individuals will present with the same features; for example – some may not have seizures. Given the small number of known patients, it is possible that additional features may be added to the list as more research emerges.
Family Stories
After 15 years of doctors appointments, lots of therapies and some orthopedic surgeries, Kate was diagnosed with FBXO31 related cerebral palsy in a research study in 2018. While it felt like a huge weight had been lifted from our shoulders after searching for answers for so long, there were still so many questions in our minds.
Kate’s early childhood was marked by developmental delays in all areas beginning at birth. We started OT feeding therapy at 2-3 months old, followed by physical therapy and speech therapy. At 12 months we starting seeing the neurologist looking for answers. Without any genetic testing available back then in 2003, she went undiagnosed for some time, when we finally landed on a Cerebral Palsy diagnosis so she could receive the services and medical care she needed. Specifically, Kate was classified with spastic diplegia cerebral palsy – with her lower body being more effected that her upper body, as well as hypotonia and some spasticity in her legs. Constant therapy including PT, OT, Speech and hippotherapy have helped Kate make slow but steady progress over time. Kate also has strabismus and cortical visual impairment and began wearing glasses at 1 year old. She was fitted with her first AFO leg braces at age 18 months, started walking with a walker and a therasuit at about 30 months and later progressed to walking short distances on her own with no walker at age 4. Hippotherapy was a big part of her learning to walk – with the horse providing the same gait pattern and helping her develop good core strength since she had very weak core muscles. Speech developed slowly and word recall was a challenge, but she was able to sing words with music more easily so we used lots of music throughout her day. She has not shown signs of regression, but learning all new skills has been significantly delayed.
Kate was followed regularly by an orthopedist due to her hip subluxation, abnormal muscle tone, and foot deformity. At about age 10, after walking independently for several years with a crouch gait, Kate’s hips and legs began to deteriorate and she needed major orthopedic surgery to re-align her hips, femurs, patellas and tibias. This was a 2 year process of surgery and major recovery, but I credit that intervention with her mobility and independence as a young adult. Today she walks short distances independently with AFOs, and uses a wheelchair for long distances. We have had to modify our home with an accessible bathroom and have a ramped entrance to our house with her bedroom on the first floor which helps Kate be as independent as possible.
Socially, Kate is very friendly, loves to connect with others, and is eager to be a part of the group and participate in all the activities around her. She is very curious about the world around her and has a good memory for details like birthdays, family routines, calendar dates and interesting facts. Kate learned best in the general education classroom alongside her typically developing peers most of the day, being pulled out for therapies and special education classes, including dyslexia based reading services to help her learn to read. She participated in inclusive social groups and sports in school as much as possible, like adaptive soccer, adaptive dance and cheer and still rides horses weekly. She joined her school’s Best Buddies program which helped her make friends and learn leadership skills and really helped with social connection in high school. Kate loves to dance, listen to music (especially Taylor Swift) , watching football, swimming and going to Starbucks with friends. Now a young adult, Kate loves her part time job at the reception desk of our local YMCA and serves as an ambassador for Best Buddies Texas.
After over a year of therapies (PT, OT, and speech) and doctor appointments, my two year old son, Madden, was diagnosed with FBXO31 in September 2024. Madden has an older brother (4, almost 5), and I had easy and uncomplicated pregnancies with both boys. Madden was born via a scheduled c-section (due to his size and my size). I started to notice that Madden was not meeting the typical milestones around 8/9 months. After months of waiting for referrals to get approved, Madden finally got placed with an early interventionist team through BabyNet (in South Carolina) when he was 14 months old. The team of doctors and doctors, who are all patient, helpful, and eager to assist, are not familiar with this genetic disorder (which I expected). We do not know what to expect, as there is so little information out there being that it is newly discovered. The geneticists, who also don’t know much about it other than what they are able to find online, are confident that the PT, OT, and speech therapies that Madden receives twice a week each for a year and a half, is all he needs. While his family and team is happy that Madden continues to progress (at his pace) and shows no signs of regression, there is much still that is unknown. Madden does not stand independently, does not walk, is an aggressive crawler, is both stiff and floppy at the same time, doesn’t communicate as a typical child his age would (he has around 10-15 words he uses regularly). He is a spirited and curious boy, who wants to be involved in everything! He craves attention and connection. He wants to engage in all of his waking hours. He is either exceedingly happy or inconsolably upset. As his mom, it is my responsibility to connect with families who are on this same journey as we are, for answers, support, and encouragement.
George’s first few months were mostly unremarkable, however starting at about 4-5 months he was starting to miss key developmental milestones. He was cross-eyed and we thought the motor delays were connected to his vision. He underwent strabismus surgery at 7 months old, but his motor delays continued. He qualified for early intervention, and we began weekly PT, OT, and ST. We were also told by our PT he was hypotonic (low tone) and to see a neurologist. After a few appointments with the neurologist that gave us no answers, we finally pushed for whole exome sequencing to give us more information. Finally, at 18 months old, he was diagnosed with the FBXO31 genetic mutation. At the time we didn’t know what that meant, but the descriptions of the few other children known to have this condition sounded incredibly similar to George.
George started sitting up on his own at about one year, and around that time we started our first physical therapy intensive session. At 2 he started talking, and around 3 he was crawling on hands and knees. He is 4 now, pulling to stand, cruising, and walks with a walker. We’ve also done two 3-week therapy intensives a year since his diagnosis. We continue to monitor his hip development and use an abduction stander multiple times a week to aid in his bone development. He wears AFOs every day as well, and uses an AAC device to assist with communication.
George is a happy, social, sweet boy and his progress, while slow, has been incredible to witness. He continues to learn and develop every day and we are confident he will walk independently one day. His language has exploded, and he has great receptive language. He loves music, dogs, other kids, and playing ball.