The identification of rare monogenic causes of neurodevelopmental disabilities has surged with advances in next-generation sequencing and broader access to genetic testing. This progress has paved the way for the development of novel disease-modifying therapies that address the root cause of these disorders rather than just managing symptoms. To prepare for patient-centered clinical trials that target meaningful outcomes for both patients and families, it is critical to bring together stakeholders, clinicians, and researchers to expand our understanding of the patient experience, natural history, genotype-phenotype relationships, and relevant biomarkers.
This symposium will explore multiple approaches to build a comprehensive knowledge base around three rare monogenic causes of neurodevelopmental disabilities—ASXL1, ASXL2, and ASXL3—collectively known as ASXL-Related Disorders (ASXL-RDs). These disorders are characterized by intellectual disability, autism spectrum disorder, severe motor impairments, and a range of medical complications including epilepsy, feeding difficulties, respiratory challenges, and vision impairment. Despite their clinical impact, current knowledge of ASXL-RDs is limited to case reports, underscoring the urgent need for richer data on patient experiences, natural history, and genotype-phenotype correlations, as well as the identification of biomarkers.
This symposium, chaired by Drs. Natasha Ludwig (neuropsychologist and sibling of an adult with ASXL3-RD) and Rujuta Wilson (behavioral child neurologist), will highlight multiple methods of qualitative and quantitative patient-experience, behavioral, and brain function data collection. These methods include focus-groups, measures of cognition, language, autism symptoms, motor function, and neurophysiological examination of brain functioning. The symposium will demonstrate how stakeholders—including researchers, clinicians, and patient families—are collaborating to meet shared research goals and ascertain clinically meaningful information about these rare genetic neurodevelopmental disorders. Featured speakers include Amanda Johnson, Executive Director of the ASXL Rare Research Endowment (ARRE) Foundation, Dr. Bianca Russell, PI of the UCLA ASXL Natural History Study (NHS), Sereen Wong, an Autism Science Foundation Fellow working with Dr. Wilson, and Dr. Abigail Dickinson, a neuroscientist. The presenters represent a diverse range of stakeholders and bring experience from longstanding research collaborations with multiple rare disease patient advocacy groups. Through these presentations, we aim to showcase how these partnerships have driven rich, multi-method data collection efforts for ASXL-RDs. Dr. Audrey Thurm will discuss how the information shared through this symposium can serve as a model for academics, clinicians, patient groups, and other stakeholders, demonstrating how successful collaboration can lay the groundwork for patient-focused data collection and clinical trial readiness.
Chair: Natasha Ludwig, Kennedy Krieger Institute,
Second Chair: Rujuta Wilson, David Geffen School of Medicine,
Discussant: Audrey Thurm, Intramural Research Program, NIMH
First Presentation: The power of a multi-stakeholder steering committee in understanding family-centered research priorities in ASXL-related disorders
Amanda Johnson, ASXL Rare Research Endowment Foundation,
Second Presentation: Enhancing Research for Rare Neurogenetic Conditions: The Role of a Centralized Patient Registry and Collaborative Data Collection During the ASXL Family Conference
Bianca Russell, David Geffen School of Medicine, Julia Sloan, David Geffen School of Medicine, University of California, Los Angeles
Rachel Northrup, Center for Neuropsychological and Psychological Assessment, Kennedy Krieger Institute
Jennea Franklin, Center for Neuropsychological and Psychological Assessment, Kennedy Krieger Institute
Isabella Capps, Center for Neuropsychological and Psychological Assessment, Kennedy Krieger Institute
Natasha N. Ludwig, Center for Neuropsychological and Psychological Assessment, Kennedy Krieger Institute, Johns Hopkins School of Medicine
Third Presentation: Multi-Modal Approach to evaluate motor function and autism symptoms in ASXL Conditions
Sereen Wong, David Geffen School of Medicine, University of California, Los Angeles
Fourth Presentation: Quantitative EEG Reveals Atypical Spectral Profiles in ASXL1-Related Disorder
Abigail Dickinson, Semel Institute of Neuroscience and Behavior, Hiroki Nariai, David Geffen School of Medicine, University of California, Los Angeles
Rosanna Weksberg, Research Institute, Hospital for Sick Children
Natasha N. Ludwig, Center for Neuropsychological and Psychological Assessment, Kennedy Krieger Institute; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine
Bianca E. Russell,