Highlights from the 2026 KSF Kabuki Syndrome Scientific Symposium
In February, the Kabuki Syndrome Foundation (KSF) hosted our biannual Kabuki Syndrome Scientific Symposium, the only meeting focused entirely on research into Kabuki syndrome. 13 researchers from around the world presented their work to over 60 attendees, covering topics ranging from basic research in various cell types to biomarkers, clinical features, and potential therapies.
We have prepared the following summary for families as an opportunity to explore the science, including supporting educational links. For more detailed information, please access the symposium abstract booklet.
Exploring Bone, Blood, and the Immune System in Kabuki Syndrome
The symposium opened with a focus on basic research to better understand how Kabuki syndrome affects bone, blood, and immune function. KMT2D, which is associated with Kabuki syndrome type 1 (KS1) was the main focus of this research, although many of these findings in downstream pathways may also be relevant to individuals with variants in KDM6A which is associated with Kabuki syndrome type 2 (KS2).
Two groups, the Shpargel (University of North Carolina at Chapel Hill) and Kwon (University of Buffalo) labs, presented on KMT2D’s role in bone-forming cells, including skeletal and craniofacial/dental development respectively. Using Kabuki syndrome mouse models with KMT2D deficiencies, both teams observed differences in cell development and function, providing insight into why some individuals with Kabuki syndrome experience fragile bones, craniofacial differences, or dental anomalies. Understanding these processes is important for clinical care decisions related to fractures or bone grafts and will inform future research.
Research on angiogenesis, the formation of blood vessels, highlighted how KMT2D influences this process. Using zebrafish and human stem cell–derived endothelial cells, investigators from the Serrano Lab (Boston University) found that KMT2D loss disrupted vascular development and reduced the ability of cells to form stable networks. Alterations in specific components of the Notch signaling pathway were implicated, suggesting this pathway plays a role in healthy blood vessel formation, may contribute to cardiovascular features of Kabuki syndrome, and therefore could be used as a downstream target for potential therapeutics.
Another presentation from the Haldar lab (University of Notre Dame) focused on microglia, the immune cells of the brain. In Kabuki syndrome mouse models, microglia were smaller and did not enter normal functional states. A triple combination therapeutic (TCF) helped these cells mature into healthy, non-activated forms, highlighting TCF as a potential therapeutic.
New Tools For Advancing Kabuki Syndrome Research
The the Heiman Lab (Boston Children’s Hospital) introduced a C. elegans model, which is a tiny worm. This model mimics the partially reduced KMT2D and KDM6A protein levels observed in individuals with Kabuki syndrome. These worms are engineered to glow when KMT2D levels are low, allowing researchers to quickly see if a treatment helps restore those levels.
This system provides a fast and cost-effective way to screen large numbers of potential therapies in living organisms and identify promising candidates for further study.
Another new tool is being developed through a KSF-funded study led by the Genevieve lab (Centre Hospitalier Universitaire de Montpellier). These researchers developed a method to fine-tune KMT2D expression in zebrafish, creating a valuable new tool for studying how reduced KMT2D activity contributes to disease mechanisms.
The researchers also examined KMT2D’s impact on immune function and behavior in zebrafish. Loss of KMT2D altered immune cell activity during wound healing and affected swimming and danger-avoidance behaviors, reflecting how the model could be used to study both the immune and neurobehavioral features of Kabuki syndrome.
Beyond KMT2D and KDM6A: The Role of Genetic Modifiers in Kabuki Syndrome
The Bjornsson lab (University of Iceland) presented findings from a KSF Discovery Grant focused on genetic modifiers in Kabuki syndrome. Using a KS1 mouse model, researchers bred the model with 52 different mouse strains to better understand how genetic background influences disease expression.
They found that some genetic backgrounds improved survival and growth, while others worsened outcomes, with notable differences between males and females. These findings mimic the varying levels in severity observed in the Kabuki syndrome community, and suggest that modifier genes play a significant role in shaping the KS1 phenotype.
This work highlights that the Kabuki syndrome phenotype is not driven solely by KMT2D or KDM6A variants, and points to modifier genes as potential new targets for future therapies.
Biomarkers for Identifying Kabuki syndrome and Measuring Therapeutic Outcomes
Advancing biomarker identification and validation for clinical trial readiness has been a key priority for KSF, driven by our Kabuki Syndrome Biomarker and Outcome Measure Consortium (KSOC). This investment was reflected in several presentations highlighting progress toward identifying and developing biomarker assays for Kabuki syndrome.
One presentation from the Youngsook Lab (Boston Children’s Hospital) identified metabolic biomarkers in plasma and urine from individuals with Kabuki syndrome, revealing over 100 metabolites differing by genotype. A specific emerged as a top candidate for both KS1 and KS2. Machine learning models were able to accurately distinguish cases from controls, and because this biomarker can be measured in urine, sample collection may be easier and less stressful for individuals with Kabuki syndrome. Ongoing studies will use KSOC samples to continue work on these metabolites.
The next presentation from the Weksberg Lab (The Hospital for Sick Children) used samples collected by KSOC to refine Kabuki syndrome DNA methylation signatures. Genome-wide profiling revealed distinct signatures for KS1 (KMT2D) and KS2 (KDM6A), including sex-specific profiles for KS2. These episignatures accurately classified cases, including variants of uncertain significance (VUS), demonstrating value for diagnosis and as a potential biomarker for clinical trials. We thank all of the families who participated in KSOC visits and donated blood samples to make this work possible.
A related study funded by KSF, in collaboration with the Weksberg lab and InnoSer Laboratories, developed a methylation signature in KS1 mice as a biomarker to monitor treatment effects. Mice were treated with an investigational drug called vafidemstat to determine if treatment could shift the KS methylation signature to look more like wild type (mice without Kabuki syndrome). The drug appeared to have an effect on the methylation signature in mice with KS, but more work needs to be done to understand its impact.
A parallel study funded by KSF, in collaboration with the Basson Lab (University of Exeter Medical School) and InnoSer Laboratories, examined gene expression in the hippocampus, a brain region involved in learning and memory. KS mice showed downregulation of many genes compared with wild type mice, meaning many genes were expressed less in the mice with KS than they were in wild type. Researchers also found treatment with the investigational drug vafidemstat increased the expression of several of these genes that are disrupted in mice with KS. We look forward to sharing more details about this exciting research as it unfolds.
Social Functioning in Kabuki Syndrome
The Banka Lab (University of Manchester) explored social functioning in people with KS1 and KS2 using caregiver questionnaires from individuals residing in the US and UK. Results highlighted challenges in social functioning, particularly around restricted interests and repetitive behaviors, while social motivation remained a relative strength. This suggests that individuals with KS enjoy social interaction but may struggle with social demands, consistent with elevated anxiety and a preference for routine. Interestingly, the researchers also noted underdiagnosis of autism within the study population, likely reflecting diagnostic overshadowing, where autistic traits may be attributed to KS rather than recognized as a co-occurring condition.
Lessons Learned from KSF’s Consortium
The final symposium presentation highlighted key lessons from KSF’s Kabuki Syndrome Biomarker and Outcome Measure Consortium (KSOC), our multisite clinical research infrastructure. These insights, spanning protocol standardization, participant-centered logistics, and approaches to better support families, will positively inform future data collection and the design of upcoming clinical studies.
Moving Research Forward Towards Treatments
Overall, the 2026 KSF Scientific Symposium showcased remarkable progress in understanding Kabuki syndrome, from fundamental disease mechanisms to biomarker development and potential therapeutic strategies. The presentations reflect an engaged, collaborative global research community committed to improving diagnosis, care, and treatment for individuals with Kabuki syndrome. This work lays a strong foundation for continued clinical advances and underscores the importance of family participation in advancing research.
Families, we invite you to join Kabuki Count, our global census and contact registry, to stay up-to-date on research and future clinical trials.
Researchers, please click here to explore our aggregated resources and sign up for updates.