This post, written by Eric Moulton, Chair-Elect of the CURE SYNGAP1 Board of Trustees, was first published on Kapable and is reprinted here with their permission and that of the author.
June is Syngap Awareness Month, making this the perfect opportunity to raise awareness about Phoebe and her fight against SYNGAP1-Related Disorders.
Phoebe was born in 2021, and she began missing gross motor milestones within months of birth. She started receiving physical therapy (PT) before her first birthday through early intervention, although other domains were not yet a concern. We were told (and hoped) that she was just late meeting some milestones and there was no serious reason to worry. Luckily, our pediatrician noticed a brief seizure during a routine check-up at 21 months. After several nights at Children’s National Hospital, Phoebe was diagnosed with epilepsy (infantile spasms) in January 2023.
During our stay, Phoebe received a genetic test that we were told would likely be inconclusive. Three weeks later, the genetic test results came back. Our lives were permanently changed when we received Phoebe’s SYNGAP1-Related Disorders (SRD) diagnosis on the 13th of February 2023.
SRD (ICD-10 F78.A1), colloquially known as SYNGAP1, is a rare genetic disorder caused by spontaneous (de novo) mutations of the SYNGAP1 gene that reduce SYNGAP1 protein levels. This protein acts as a regulator in the synapses (where neurons communicate with each other). When SYNGAP1 protein levels are too low, we see an increase in excitability in the synapses, making it difficult for neurons to communicate effectively.
This leads to the many neurological symptoms seen in SRD patients, including global developmental delay leading to intellectual disability, epilepsy, severe behaviors and autism spectrum disorder (ASD), hypotonia (low muscle tone), gross and fine motor delays, significant speech and language deficits, disordered sleep, and chronic gastrointestinal (GI) challenges.
Phoebe suffers from all of these. SRD is considered a Developmental and Epileptic Encephalopathy (DEE). Beyond being a neurodevelopmental disease, the constant epileptic activity in Phoebe’s brain actively worsens developmental outcomes. In a typical SRD trajectory, both the epilepsy and behaviors/autism become more severe over time.
Phoebe is now counted among the over 1,700 identified global patients fighting this awful disease (more than 500 in the US, and several in the DC region), and the number grows weekly as genetic testing increases (the only way to diagnose SRD). As a result of her disease, Phoebe receives Physical, Occupational, Speech, and Applied Behavior Analysis (ABA) therapies. She takes prescription medication for seizures and behaviors in addition to over-the-counter medication for sleep and GI issues. Phoebe has endured multiple overnight EEGs and has made six visits (and counting) to Children’s Hospital of Philadelphia (CHOP) as part of an ongoing SYNGAP1 Natural History Study. Like far too many SRD patients, Phoebe is also now in the school placement process in the hopes of finding a school that can accommodate her multiple disabilities.
While it is easy to only focus on the negatives, Phoebe is truly loved by her family and community. She lights up around her family, friends, teachers, and therapists. She has a beautiful smile and a mischievous personality that shines through in her actions. Phoebe loves playing in water, whether it’s a sink, bath, pool, or ocean. Her favorite animals are frogs and pigs. She also loves music and is currently discovering the wide world of Disney movies and songs.
Along with music, Phoebe loves to dance, and she has been enrolled in an adaptive dance class since September 2023 (before she could even walk). That said, every day of Phoebe’s life is a fight. She has been fighting multiple daily seizures, which have re-emerged. She has been fighting hypotonia, which prevents her from walking, running, and jumping. She has been fighting self-injurious behaviors, such as headbanging, biting, and attempting to expose herself to extreme heat. She has been fighting to communicate with us so she can be understood and have her needs met. She has been fighting sensory processing problems, which make the world loud, uncomfortable, and frightening on a constant basis. And, increasingly and heartbreakingly, Phoebe has been fighting social isolation due to SRD.
Phoebe is only five years old, and without effective treatment, her fight will only get harder every day of her life. Luckily, we found the CURE SYNGAP1 patient advocacy group and community within days of diagnosis. Our family has worked alongside CURE SYNGAP1 for over three years now to fight for Phoebe and the global SRD community. This month, we are working to raise awareness about Phoebe’s fight and the fight all other SRD patients endure. We fight for scientists and pharmaceutical companies to invest more time and resources into curing SRD. We fight to get clinical trials off the ground. We fight to get support for the families and patients who are struggling against this disease every day. We need to fight for Phoebe and every other current and future patient so they can finally stop fighting and live.
We are very thankful for all the love and support shown by friends, family, and the community. We would not be where we are without it. Phoebe does not know she is sick; she just wakes up every single day of her life and fights like the warrior she is. We cannot stop fighting either. Phoebe needs us all. We must do everything we can to cure SYNGAP1.
