Adult Phenotype of Associated Disorders
Abstract number :
1.093
Submission category :
11. Behavior/Neuropsychology/Language / 11A. Adult
Year :
2024
Submission ID :
912
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Marlene Rong, MSc – Adult Genetic Epilepsy (AGE) Program, Toronto Western Hospital, University Health Network
Presenting Author: Quratulain Zulfiqar Ali, MD – Adult Genetic Epilepsy (AGE) Program, Toronto Western Hospital, University Health Network/University of Toronto
Ángel Aledo-Serrano, MD, PhD – Epilepsy and Neurogenetics Unit, Vithas Madrid La Milagrosa University Hospital, Madrid, Spain Neurology Department, Ruber Internacional Hospital, Madrid, Spain
Allan Bayat, MD, PhD – Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Filadelfia, Dianalund, Denmark
Orrin Devinsky, MD – NYU Grossman School of Medicine
Farah Qaiser, MSc – Adult Genetic Epilepsy (AGE) Program, Toronto Western Hospital, University Health Network
Ilakkiah Chandran, MSc Candidate – Adult Genetic Epilepsy (AGE) Program, Toronto Western Hospital, University Health Network
Anum Pirani, BScN – Adult Genetic Epilepsy (AGE) Program, Toronto Western Hospital, University Health Network
Alfonso Fasano, MD, PhD, FAAN – Edmond J. Safra Program in Parkinson’s Disease
Anne Bassett, MD, FRCPC – Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
Danielle Andrade, MD, MSc, CSCN (EEG) – Adult Genetic Epilepsy (AGE) Program, University of Toronto, Toronto Western Hospital, University Health Network
Rationale: Pathogenic CHD2 variants are associated with neurodevelopmental disorders (NDDs) and developmental and epileptic encephalopathy (DEE). While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with CHD2 variants.
Methods: Patients 18 years or older with likely pathogenic or pathogenic (LP/P) CHD2 variants were recruited via physicians’ practices and patient organization groups. We used standardized tools to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder and adaptive behavioural skills of patients.
Results: Fourteen unrelated adult patients (age range: 18-45 years, median: 21 years) with LP/P CHD2 variants were described. Eleven novel variants were identified. No genotype-phenotype correlations were identified. Seventy-nine percent of adults still have ongoing seizures requiring pharmacological treatment and neurostimulation in 28%. Photosensitivity was present in 64% of adult patients. Autism spectrum disorder (ASD) was diagnosed in 71% of patients. Only 43% could ambulate independently. Behavioural issues were reported in 100% of adult patients, and 71% had internalizing features such as anxiety. Reflux was present in 36% of patients, constipation in 71%, 43% of patients had abnormal nociception. No patient was completely independent to perform basic activities of daily living. Higher seizure severity was associated with worse non-seizure outcomes (p=0.04). The oldest patient was aged 45 years with behavioural issues, autism spectrum disorder but no seizures.
Conclusions: Most adults with CHD2 continue to have seizures, and seizure severity is associated with worse comorbidities such as maladaptive behaviours, gait, gastrointestinal, sleep, and nociception problems. Longevity has not been systematically studied in this group of patients, but the oldest alive patient is described here, at the age of 45 years. These data may provide prognostic insights for families of pediatric patients as well as help identify key points to be addressed in precision trials for patients with CHD2.
Funding: None
Behavior