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.
In addition to clinical features previously reported with STXBP1-related disorders such as developmental delay (n=240 references), behavior (n=201) and seizures (n=147), the researchers identified previously underreported symptoms including gastrointestinal symptoms (n=68), respiratory symptoms (n=24) and pain (n=30). These symptoms tended to impact autonomy, socialization and schooling. In addition, caregivers for patients with STXBP1-related disorders felt an impact on their emotions, their level of support, and daily life and activities. Seizures were more commonly referenced when patients were infants, and socialization concerns were referenced more commonly in childhood years.
“When providing care for genetic epilepsies, we need to make sure that we are focusing on what is important to our patients and their caregivers,” said senior study author Ingo Helbig, MD, a pediatric neurologist in the Division of Neurology and co-director of ENGIN at CHOP. “In addition to describing the full range of the lived experienced, our study also captured an important difference between healthcare providers and caregivers, which shows just how important it is to make sure the people who deal with these conditions every single day have their voices heard.”
This study was supported by an Individual Biomedical Research Award from The Hartwell Foundation, the National Institute for Neurological Disorders and Stroke grant K02 NS112600, the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Intellectual and Developmental Disabilities Research Center (IDDRC) at Children’s Hospital of Philadelphia and the University of Pennsylvania grant U54 HD086984, and by intramural funds of the Children’s Hospital of Philadelphia through the Epilepsy NeuroGenetics Initiative (ENGIN). Research was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878, the Institute for Translational Medicine and Therapeutics’ (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics at the Perelman School of Medicine of the University of Pennsylvania, the German Research Foundation grants HE5415/3-1, HE5415/5-1, HE5415/6-1, We4896/4-570 1, and He5415/7-1 and by the Genomics Research and Innovation Network.
Sullivan et al, “A disease concept model for STXBP1-related disorders.” Epilepsia Open. Online January XX, 2023. DOI: TK
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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.
In addition to clinical features previously reported with STXBP1-related disorders such as developmental delay (n=240 references), behavior (n=201) and seizures (n=147), the researchers identified previously underreported symptoms including gastrointestinal symptoms (n=68), respiratory symptoms (n=24) and pain (n=30). These symptoms tended to impact autonomy, socialization and schooling. In addition, caregivers for patients with STXBP1-related disorders felt an impact on their emotions, their level of support, and daily life and activities. Seizures were more commonly referenced when patients were infants, and socialization concerns were referenced more commonly in childhood years.
“When providing care for genetic epilepsies, we need to make sure that we are focusing on what is important to our patients and their caregivers,” said senior study author Ingo Helbig, MD, a pediatric neurologist in the Division of Neurology and co-director of ENGIN at CHOP. “In addition to describing the full range of the lived experienced, our study also captured an important difference between healthcare providers and caregivers, which shows just how important it is to make sure the people who deal with these conditions every single day have their voices heard.”
This study was supported by an Individual Biomedical Research Award from The Hartwell Foundation, the National Institute for Neurological Disorders and Stroke grant K02 NS112600, the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Intellectual and Developmental Disabilities Research Center (IDDRC) at Children’s Hospital of Philadelphia and the University of Pennsylvania grant U54 HD086984, and by intramural funds of the Children’s Hospital of Philadelphia through the Epilepsy NeuroGenetics Initiative (ENGIN). Research was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001878, the Institute for Translational Medicine and Therapeutics’ (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics at the Perelman School of Medicine of the University of Pennsylvania, the German Research Foundation grants HE5415/3-1, HE5415/5-1, HE5415/6-1, We4896/4-570 1, and He5415/7-1 and by the Genomics Research and Innovation Network.
Sullivan et al, “A disease concept model for STXBP1-related disorders.” Epilepsia Open. Online January XX, 2023. DOI: TK
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Epilepsy Neurogenetics Initiative (ENGIN)