Sara Morcos1, Kristin Falbo1, Laurie Seltzer1, David Bearden2
1University of Rochester School of Medicine and Dentistry, 2University of Rochester School of Medicine
Objective:
To conduct a natural history study understanding YWHAG-associated epilepsy in children.
Background:
The YWHAG gene encodes a member of the 14-3-3 protein family important for cellular signaling and neuronal migration. Recent studies suggest its role in early-onset epilepsy, epileptic encephalopathy, and seizures in children. However, the natural history of this disorder has not been described. We report the largest prospective study to date in children with YWHAG-associated Neurodevelopmental Disorders (YWHAG-NDD).
Design/Methods:
The YWHAG Natural History Study (YWHAG-NHS) is a prospective, single site, non-randomized, longitudinal study of individuals with neurodevelopmental disorders and/or seizures secondary to pathogenic variants in YWHAG. Participants were assessed via video visits, review of medical records, neuroimaging, and electroencephalograms. Adaptive function was assessed using the Vineland-3 Adaptive Behavior Scales. This paper presents baseline data on the first 20 participants in the study, characterizing the clinical presentation, natural history, and response to treatment of epilepsy in YWHAG-NDD.
Results:
We identified 20 participants with YWHAG-NDD. 95% presented with seizures, while one patient presented solely with developmental delays. The most commonly reported seizure types included generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. 60% of participants reported seizures in the setting of fever. 55% of participants reported treatment resistant epilepsy and 40% reported at least one episode of status epilepticus. Other notable clinical manifestations included delays in language skills, cognition, social skills, and motor skills.
Conclusions:
This study helps elucidate the natural history of YWHAG-NDD. Future research should focus on identifying optimal treatments in children with YWHAG-NDD and treatment resistant epilepsy, and in optimizing developmental outcomes in this population
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