Article published by CHOP
Researchers from the Epilepsy Neurogenetics Initiative (ENGIN) at Children’s Hospital of Philadelphia (CHOP) have created a comprehensive disease model for one of the most common genetic causes of childhood epilepsies and neurodevelopmental disorders. By systematically mapping symptoms and assessing their impacts on patients and their caregivers, the researchers identified previously underreported symptoms beyond just neurological symptoms. These results may serve as an important foundation for future trials assessing the effectiveness of therapeutic interventions for all related symptoms. The findings were recently published online in Epilepsia Open.
Disorders related to changes in the STXBP1 gene represent a group of common genetic epilepsies and neurological disorders. However, the variety of symptoms associated with this group of diseases is poorly understood, especially those that extend beyond neurological symptoms. In order to better understand how these diseases were impacting patients, the researchers wanted to develop a formal framework that assessed the actual experience of patients and their families. This so-called disease concept model is meant to determine which outcomes are relevant in everyday clinical practice.
“Many clinical studies are often limited to predefined symptoms like seizures or developmental milestones, and as such, these studies could be missing valuable information about an aspect of the disease that could be treated and significantly improve a patient’s quality of life,” said first study author Katie Rose Sullivan, a clinical genetic counselor with ENGIN at CHOP. “Disease concept models have been developed for other neurological disorders and have contributed significantly to our understanding of overall symptom burden, so we sought to do the same for STXBP1-related disorders, one the most common genetic epilepsies diagnosed in children.”
The researchers performed more than 24 hours of interviews among 19 caregivers of 16 individuals with STXBP1-related disorders and seven healthcare professionals. This resulted in a total of 3626 references to 38 distinct clinical concepts, covering the entire range of reported symptoms. Based on this information, the researchers systematically coded themes and grouped concepts into symptoms, symptom impact, and caregiver impact, then quantified the frequency of these concepts throughout the lifespan and across various clinical subgroups.