Search Results (2)

Background: The goal of the study was to describe the visual function characteristics of children with developmental epileptic encephalopathy resulting from mutations in the STXBP1 gene. Methods: The study included 26 consecutive patients from the Polish STXBP1 population (11 male and 16 female; mean age: 7 years and 4 months; SD 4.03; range: 2–16 years) evaluated at a single center for strabismus and binocular vision. Data were obtained from medical records, including ophthalmological, neurological, and genetic information, as well as orthoptic and ophthalmological examinations performed in the clinic. Results: No major eye disorders were identified during the ophthalmological evaluation. The average prevalence of hyperopia was 76.9% (mean for OD, OS), with hyperopia above 4.25 D occurring in 17.3% (n = 4) of participants. Astigmatism was present in 96.2% of patients, with values ≥ 2.75 D in 27% (n = 7) of the group. The mean disc–foveal angle across all subjects was 7.23° ± 6.85° (range: −10.34° to 19.77°). Convergence was absent in 53.8% (n = 14) of patients. Mean accommodation responses equal to or higher than +1.0 D in any eye were noted in 90.5% of subjects. The mean accommodative/convergence (AC/A) ratio was 1.16 (SD 1.05; range: 0–3.3). Fusion was diagnosed using the 20 base-out prism test in 77% (n = 20) of patients, of which 85% (n = 17) had a positive response. Conclusions: This is the first study to comprehensively assess visual function in children with STXBP1 synaptopathy. Binocular vision development in individuals with STXBP1 differs from that of the general population. Considering the high prevalence of refractive errors, deficits in accommodation, and a low AC/A ratio, early visual diagnostics and the use of corrective eyewear are recommended in these patients. Full article

Lennox–Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Current treatments primarily focus on symptom management through antiseizure medications (ASMs), dietary therapy, epilepsy surgery, and neuromodulation, but often fail to address the underlying pathophysiology or improve cognitive outcomes. As genetic causes are identified in 30–40% of LGS cases, precision therapeutics targeting specific molecular mechanisms are emerging as promising disease-modifying approaches. This narrative review explores precision therapeutic strategies for LGS based on molecular pathophysiology, including channelopathies (SCN2A, SCN8A, KCNQ2, KCNA2, KCNT1, CACNA1A), receptor and ligand dysfunction (GABA/glutamate systems), cell signaling abnormalities (mTOR pathway), synaptopathies (STXBP1, IQSEC2, DNM1), epigenetic dysregulation (CHD2), and CDKL5 deficiency disorder. Treatment modalities discussed include traditional ASMs, dietary therapy, targeted pharmacotherapy, antisense oligonucleotides, gene therapy, and the repurposing of existing medications with mechanism-specific effects. Early intervention with precision therapeutics may not only improve seizure control but could also potentially prevent progression to LGS in susceptible populations. Future directions include developing computable phenotypes for accurate diagnosis, refining molecular subgrouping, enhancing drug development, advancing gene-based therapies, personalizing neuromodulation, implementing adaptive clinical trial designs, and ensuring equitable access to precision therapeutic approaches. While significant challenges remain, integrating biological insights with innovative clinical strategies offers new hope for transforming LGS treatment from symptomatic management to targeted disease modification. Full article