Dixon-Salazar, T. | Search bioRxiv

bioRxiv2026

Sleep Health in Lennox-Gastaut Syndrome impacts both Individuals with LGS and their Caregivers

Sleep disturbances are a significant but underrecognized burden for individuals with Lennox-Gastaut Syndrome (LGS) and their caregivers. We conducted a large LGS caregiver survey to assess sleep quality, duration, specific sleep-related issues, and management strategies. Quantitative analysis revealed a significant association between nocturnal seizures and overall seizure frequency, but general sleep metrics in individuals with LGS (e.g., sleep hours, sleep quality) were not associated with seizure burden. In contrast, caregiver sleep was frequently disrupted - particularly in families who co-slept or reported frequent seizures. Nearly 40% of caregivers experienced nightly sleep disturbances. Respondents reported a range of strategies to manage sleep problems, including medication, environmental adjustments, and behavioral routines. Many also expressed frustrations over the limited effectiveness of strategies and inadequate support for sleep issues. These findings underscore the dual impact of LGS-related sleep disturbances on patients and caregivers, and highlight the need for comprehensive, family-centered approaches to sleep health.

neuroscience↗

bioRxiv2019

Ultra-rare genetic variation in the epilepsies: a whole-exome sequencing study of 17,606 individuals

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,364 controls of European ancestry. We focused on three phenotypic groups; the rare but severe developmental and epileptic encephalopathies (DEE), and the commoner phenotypes of genetic generalized epilepsy (GGE) and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy, with the strongest enrichment seen in DEE and the least in NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, while no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEE and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the top associations, including CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study confirms a convergence in the genetics of common and rare epilepsies associated with ultra-rare coding variation and highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology in the largest epilepsy WES study to date.

genetics↗