Get to Know the FBXO28 Research Foundation

When my daughter was diagnosed with a de novo FBXO28 variant, I found myself facing an ultra-rare disorder with very little published information, no established natural history, no dedicated patient organization, and no disease-modifying treatment. As a physician, I could understand the medical terminology and scientific literature, but that did not make the uncertainty any easier as a parent. I began by trying to answer the questions any mother would ask: What does this diagnosis mean for my child? What can we expect? Is there anything we can do? Could there ever be a treatment? Those questions gradually turned into action and eventually into an international effort to find answers for families affected by FBXO28.

About FBXO28-Related Neurodevelopmental Disorder

FBXO28-related neurodevelopmental disorder, also known as developmental and epileptic

encephalopathy 100 (DEE100), is an ultra-rare genetic neurodevelopmental condition caused by pathogenic variants in the FBXO28 gene. FBXO28 encodes an F-box protein involved in SCF ubiquitin-ligase complexes and protein regulation. The association between FBXO28 and neurodevelopmental disease was first reported in 2018, and the disease spectrum was expanded in 2021 when nine additional individuals were described.

Reported features include global developmental delay, intellectual disability of variable severity, hypotonia, impaired or absent speech, motor impairment, movement disorders, and epilepsy. However, the emerging phenotype appears broader and more variable than the earliest descriptions, and not every individual experiences the same epilepsy severity or developmental course. The true incidence and prevalence remain unknown, with only a very small number of affected individuals reported in the medical literature. There is currently no disease-modifying or gene-targeted treatment for FBXO28-related disorder.

Our Journey

FBXO28-related neurodevelopmental disorder is a multisystem condition in which epilepsy is only one part of the overall disease burden. Common features include developmental and intellectual disability, hypotonia, limited or absent speech, impaired motor development, and difficulties with coordination or independent mobility. Some individuals also experience movement disorders or visual problems, while epilepsy can range from absent or relatively manageable seizures to severe developmental and epileptic encephalopathy. Reported seizure types include epileptic spasms, myoclonic, tonic, focal, and generalized seizures.

For families, the lived experience extends far beyond seizure counting. Feeding and swallowing difficulties, reflux, sleep disturbance, respiratory problems, orthopedic complications, and developmental regression can also occur. Families may navigate frequent neurological and genetic assessments, EEGs and imaging, developmental therapies, medication trials, and uncertainty about future development. Because so few patients are known, families often have limited information about prognosis or what symptoms may emerge next.

Our Mission

The FBXO28 Research Foundation was created to build the research infrastructure that did not yet exist for this disorder. We are identifying and connecting affected families internationally, assembling a patient cohort, developing clinician and parent questionnaires for systematic phenotyping and natural history data collection, and establishing patient-derived fibroblast and iPSC resources that can be shared with researchers.

Research is central to our work. We are bringing together scientists and clinicians from different countries and disciplines to pursue molecular characterization, transcriptomics and proteomics, neuronal and synaptic phenotyping, animal models, and potential therapeutic directions including RNA-based therapies, gene editing, and drug repurposing. Our goal is to create the knowledge, tools, and collaborations needed to better understand FBXO28 and explore what may eventually be therapeutically possible.

I am Especially Proud of...

I am especially proud of how quickly we have transformed an ultra-rare diagnosis into an active international research effort. Our greatest achievement is not any single experiment or collaboration, but creating momentum where previously there was very little. FBXO28 may affect only a small number of known individuals worldwide, but those patients now have the beginnings of a coordinated research community working to understand the disease and explore potential therapeutic approaches. Building that bridge between families and science from the ground up is what I am most proud of.

Excited for REN Because...

For an ultra-rare disorder like FBXO28-related neurodevelopmental disorder, collaboration is essential. We hope REN will help us learn from organizations that are further along this journey and build on solutions already developed within the rare epilepsy community. We are particularly interested in collaboration around natural history studies and patient registries, meaningful clinical outcome measures, research strategy, preclinical development, regulatory pathways, fundraising, and engagement with biotechnology and pharmaceutical partners.

We are also excited to connect with researchers, clinicians, and patient organizations working across developmental and epileptic encephalopathies. Many of the scientific challenges we face are shared across rare epilepsies, making the collective experience of the REN community especially valuable. Ultimately, we hope REN can help us build a smarter and faster translational pathway for FBXO28 while allowing us to contribute what we learn back to the network.

A Personal Note

My journey to FBXO28 began as a mother, not as the founder of a foundation. After my daughter's diagnosis, I began searching for other families, contacting scientists who had

studied FBXO28, and reaching out to researchers working on disease models and therapeutic technologies. One conversation led to another, and what began as an attempt to understand my daughter's diagnosis gradually became an international effort to build a research program around this condition.

My motivation is deeply personal, but it has grown beyond my own daughter. Every new family we find reminds me that other parents are facing the same uncertainty and asking the same questions. Developing a therapy for an ultra-rare neurodevelopmental disorder is extraordinarily difficult and there are no guarantees, but I strongly believe that rarity should not mean a disease is left unexplored. My hope is that we can turn uncertainty into knowledge, knowledge into therapeutic possibilities, and individual families scattered around the world into a community that no longer has to face FBXO28 alone.

________

By Aleksandra Sułkowska-Bojarczyk, Founder, FBXO28 Research Foundation