Advances in epilepsy associated with 16p11.2 microdeletion syndrome

Abstract

Background

16p11.2 microdeletion syndrome is a genetic disorder with a population prevalence of approximately 2.84.3 per 100,000 individuals. Epilepsy is one of its core symptoms, significantly impacting neurodevelopment and quality of life. Current treatment strategies are shifting from empirical antiepileptic drug use toward mechanism-based precision therapy. Epilepsy in this syndrome typically presents in infancy, with focal seizures as the most common type.

Methods

Electroencephalogram findings often include focal or multifocal epileptiform discharges. Genomic deletions affecting key genes such as PRRT2, KCTD13, TAOK2, QPRT, and SEZ6L2 contribute to neurodevelopmental abnormalities, synaptic dysfunction, and excitatory-inhibitory imbalance through dysregulated molecular pathways including RhoA signaling, microtubule dynamics, and quinolinic acid metabolism.

Conclusions

Clinically, levetiracetam shows limited efficacy in PRRT2-related epilepsy, whereas valproate, oxcarbazepine, and topiramate are often effective. Emerging therapeutic strategies target specific molecular mechanisms, such as RhoA inhibition or modulation of the kynurenine pathway. The integration of genetic diagnosis with pathway-specific interventions offers promising avenues for improving seizure control and neurodevelopmental outcomes in patients with 16p11.2 microdeletion syndrome. In this article, we review the clinical features.molecular mechanisms and therapeutic strategies of 16p11.2 microdeletion.associated epilepsy to provide a theoretical basis for precision diagnosis and treatment.