KCNQ1 polymorphisms shown to be associated with increased risk for T2DM in the recent GWA study might also represent genetic factors contributing to the development of GDM in Koreans.

Background and Objectives:TheSLC35A2gene, located at chromosome Xp11.23, encodes for a uridine diphosphate (UDP)-galactose transporter. We describe clinical, genetic, neuroimaging, EEG and histopathological findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somaticSLC35A2gene variants.Methods:This is a retrospective multicenter study where we performed a descriptive analysis and classical hypothesis testing. We included the variables of interest significantly associated with the outcomes in the generalized linear models.Results:Two main phenotypes were associated with brain somaticSLC35A2variants: 1) early epileptic encephalopathy (EE, 39 patients) with epileptic spasms as the predominant seizure type and moderate to severe intellectual disability, and 2) drug-resistant focal epilepsy (DR-FE, 8 patients) associated with normal/borderline cognitive function and specific neuropsychological deficits. Brain MRI was abnormal in all patients with EE and in 50% of those with DR-FE. Histopathology review identified mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) in 44/47 patients and was inconclusive in three. The 47 patients harbored 42 distinct mosaicSLC35A2variants, including 14 (33.3%) missense, 13 (30.9%) frameshift, 10 (23.8%) nonsense, four (9.5%) in-frame deletions/duplications, and one (2.4%) splicing variant. Variant allele frequencies (VAF) ranged from 1.4 to 52.6% (mean VAF: 17.3±13.5).At last follow-up (35.5± 21.5 months), 30 patients (63.8%) were in Engel class I, of which 26 (55.3%) were in class IA. Cognitive performances remained unchanged in most patients after surgery. Regression analyses showed that the probability of achieving both Engel class IA and class I outcomes, adjusted by age at seizure onset, was lower when the duration of epilepsy increased and higher when postoperative EEG was normal or improved. Lower brain VAF was associated with improved postoperative cognitive outcome in the analysis of associations, but this finding was not confirmed in regression analyses.Discussion:Brain somaticSLC35A2gene variants are associated with two main clinical phenotypes, EE and DR-FE, and a histopathological diagnosis of MOGHE. Additional studies will be needed to delineate any possible correlation between specific genetic variants, mutational load in the epileptogenic tissue and surgical outcomes.

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Purpose: Lamotrigine (LTG) is often used as adjunctive therapy in Lennox-Gastaut syndrome (LGS); however, it may worsen myoclonic and atypical absence seizures in LGS patients. This study reviewed the overall efficacy and safety of LTG in children with LGS.Methods: This retrospective study included 38 patients (aged <18 years) with LGS who underwent LTG adjunctive therapy between October 2020 and March 2022 at Severance Children’s Hospital. The primary outcome was the change in seizure frequency at 3, 6, and 12 months after starting LTG treatment. A favorable treatment response was defined as a ≥50% reduction in seizure frequency.Results: The main seizure semiology at the start of treatment was tonic-clonic in 15 (39.5%) patients, spasm in 14 (36.8%), atonic in five (13.2%), myoclonic in three (7.9%), and absence in one (2.6%). The median number of anti-seizure medications (ASMs) was 3.95 (interquartile range, 3 to 4.75). The most common concomitant ASMs were valproate (35/38, 92.1%), levetiracetam (23/38, 60.5%), and topiramate (20/38, 52.6%). After 3 months, seizure frequency was reduced by >50% in 47.4% of patients (18/38). After 6 months, 20 patients (20/36, 55.6%) showed a favorable response. After 12 months, five patients (5/11, 45.5%) responded to treatment. Three patients showed myoclonic seizures at the start of treatment and >50% amelioration in seizure frequency at the 3- and 6-month follow-up visits.Conclusion: This study reaffirms the efficacy and safety of LTG in children with LGS. Therefore, LTG is strongly recommended as an adjunctive therapy for children with LGS.