Developmental epileptic encephalopathy in DLG4-related synaptopathy.

Area of Science:

• Neuroscience
• Genetics
• Epileptology

Background:

• DLG4 pathogenic variants cause DLG4-related synaptopathy, a condition with diverse neurological features.
• Epilepsy affects approximately 50% of individuals with DLG4-related synaptopathy but has not been extensively studied.
• Understanding the epilepsy spectrum is crucial for comprehensive patient management.

Purpose of the Study:

• To investigate the phenotypic spectrum of epilepsy and associated comorbidities in individuals with DLG4-related synaptopathy.
• To characterize seizure types, developmental epileptic encephalopathy (DEE), and related sleep disturbances.
• To explore potential genotype-phenotype correlations.

Main Methods:

• A multicenter study included 35 individuals with DLG4 variants and epilepsy.
• Clinical data on neurodevelopmental status, motor function, and comorbidities were collected.
• Electroencephalography (EEG), video-polygraphy, and brain MRI data were analyzed; antiseizure medication response was assessed retrospectively.

Main Results:

• Focal seizures were the most common seizure type among the diverse presentations.
• Developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in over 25% of individuals.
• Regression in motor or verbal domains was observed, particularly in those with ESES/DEE-SWAS; no clear genotype-phenotype correlation was found.

Conclusions:

• DEE is confirmed as part of the DLG4-related synaptopathy phenotypic spectrum.
• Approximately one-fourth of affected individuals present with ESES/DEE-SWAS, necessitating thorough investigation with sleep EEG.
• This study underscores the significant impact of epilepsy on DLG4-related synaptopathy and guides further diagnostic approaches.