Clinical trajectories and medication response in TBC1D24-related epilepsies.
Publication/Presentation Date
11-10-2025
Abstract
OBJECTIVE: Biallelic variants in TBC1D24 represent a rare cause of epilepsy and neurodevelopmental disorders, including severe developmental and epileptic encephalopathies. Here, we present the first attempt to delineate the longitudinal disease histories and effectiveness of antiseizure medications (ASMs) in TBC1D24-related disorders.
METHODS: We performed an analysis of the electronic medical record data of 15 individuals with TBC1D24-related disorders. Using the Human Phenotype Ontology, we recorded neurological histories and medication responses across 197 patient-years of information.
RESULTS: Individuals with TBC1D24-related disorders presented with a range of seizure types with a median age at seizure onset of 3 months-most frequently (73%) with focal myoclonic seizures both sparing and impairing consciousness. We report the maximum prevalence (MP) of various features as percentages of individuals reporting a given phenotype at that time point, compared to all those with available data at that time point. MP of focal seizures was at 6.25 and 7.75 years of age (88%), myoclonic seizures (focal and generalized) between 9 and 10 years of age (80%), and status epilepticus at 9 and 11 months of age (90%). Individuals also presented with a range of movement disorders. The MP of non-epileptic myoclonus was 100% at 1 and 17 months of age, tremor at 14 months of age (67%), ataxia at 7.25 years of age (45%), and episodic hemiplegia at 3.25 years of age (20%). The use of phenobarbital, oxcarbazepine, and topiramate showed the most promise in seizure management when compared to other ASMs. Everolimus, phenobarbital, and oxcarbazepine proved more effective in maintaining seizure freedom or reducing seizure frequencies in focal and myoclonic seizures compared to other ASMs.
SIGNIFICANCE: TBC1D24-related disorders are characterized by severe and pharmacoresistant epilepsy, with status epilepticus, focal seizures, and myoclonic seizures early in life. This study offers novel insights into the longitudinal disease course and treatment response in TBC1D24-related disorders, a critical first step toward clinical trial readiness.
ISSN
1528-1167
Published In/Presented At
Mondragon, E., Magielski, J. H., Bane, B., Nolan, J., Ruggiero, S. M., Armstrong, D., Arnold, S., Sirsi, D., Helbig, I., & McKee, J. L. (2025). Clinical trajectories and medication response in TBC1D24-related epilepsies. Epilepsia, 10.1111/epi.70013. Advance online publication. https://doi.org/10.1111/epi.70013
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
41215607
Department(s)
Department of Pediatrics
Document Type
Article