Hello all… We are a family of five and live in Colorado in the United States. We have been blessed with three beautiful children, our oldest of whom has the MAPK8IP3 gene variant. Life is a bit crazy with three teenagers who keep us on our toes!
Our journey with Matthew (18 years old) has been full of ups, downs, twists, and turns, and we never really know exactly what is in store next! He has taught us so much about hard work, determination, patience, and embracing each day and everyone he meets with open arms and a huge smile! His personality is larger than life, and his charismatic charm is arguably one of his best qualities!
We didn’t really know anything was atypical with Matthew until he was about eight to ten months old. I was in a new mom’s group, and all the other babies were sitting up, crawling, pulling to a stand, starting to walk, etc. Matthew would just be a big happy “blob” sitting in his bouncy seat watching — totally content. He just had no interest in trying to move, but he was happy, alert, and ate and slept well. The doctor told us we had to wait until 18 months before we could see a specialist because “the range of normal was 9-18 months.” Well, at 18 months old, when he was barely talking and not walking or standing yet, I stormed in and demanded referrals to specialists to find out if something was “wrong.”
We started all genetic testing and seeing specialists at 20 months old (this was back in 2004). All genetic testing at that point came back negative, but his first MRI of the brain showed myelination issues and an under-developed cerebellum. The neurologists also documented things like hypotonia and cerebellar ataxia. He immediately began an intensive early intervention program at 22 months. In addition to the therapies at this state program, he also started private physical therapy, occupational therapy, and speech therapy every week. We continued these therapies weekly for basically his entire life (he still does all of these now but has also added weekly massage therapy, music therapy, and behavior therapy).
He has worn AFOs or SMOs his entire life, and learned to walk with a four-legged walker. He took his first independent steps a couple months after turning three. He didn’t run until he was about 12 years old, and even now it is awkward and different, but he can run fast, which we never thought he would be able to do. He still can’t jump, climb, gallop, etc. and his balance and coordination are significantly impaired. He can’t stand on one foot for more than three to five seconds, and he does lose his balance at times and falls down occasionally (though not nearly as much as he did when he was younger). He is much more ataxic first thing in the morning and at night before bed when he is fatigued. However, he still loves to play adaptive sports, including baseball (his #1 love), basketball, and soccer, and he is great swimmer (with flippers)! It is a true thrill to see him play these sports to the best of his physical abilities — it is a kind of appreciation that few people get the privilege to experience!
For the first 10 years of his life, Matthew’s primary clinical symptoms were the physical or motor limitations — both fine and gross motor and speech and language. His receptive language was always better than his expressive. We know there is so much more in his brain than he can express, and unlocking the treasure of what he has inside has always been a goal! He has always been verbal but language and speech articulation are significantly delayed. As he got older and hit adolescence, we noticed more of the behavior issues, autistic traits, and cognitive limitations. BUT, he has a contagious personality that you can’t help but fall in love with! He is super friendly and loves being around people, especially his family.
Today, at 18 years old, he has the following diagnoses: Apraxia, Intellectual Disability, Cerebellar Ataxia, Abnormal Brain Iron Accumulation, and Autism. He most likely will not be able to live independently and will require significant supports his entire life. Our dream for him is to find a supportive residential community for adults with intellectual disabilities so that he can live as independently as possible and have true friends of his own who navigate life together.
As far as the MAPK8IP3 gene variant goes, we waited over 15 years to finally understand the cause for Matthew’s neurological disorders and clinical symptoms. After years of targeted genetic testing and everything coming back negative, we finally did total exome sequencing in 2017. Through this exome sequencing, the lab found the gene variant in Matthew’s genetic make-up, but at the time the gene was “uncharacterized,” meaning it hadn’t been studied in humans yet. It wasn’t until 2019 when an article called De Novo Variants in MAPK8IP3 Cause Intellectual Disability with Variable Brain Anomalies was published in The American Journal of Human Genetics by a German scientist who studied the MAPK8IP3 gene further in humans (of which our son was one of 13 specimens in the study) that we were able to definitively say that Matthew’s 1-bp deletion in the MAPK8IP3 gene on chromosome 16p13 is the cause of his neurodevelopmental disorders.