Objective: To evaluate the impact of cannabidiol (CBD) on quality of life (QoL) in children with drug-resistant epilepsy at Amiens Picardie University Hospital (France), with seizure control as a secondary outcome.Methods: This single-center, retrospective observational study included 30 children aged 3–18 years with drug-resistant epilepsy treated with CBD. Quality of life was assessed before and after treatment using the QOLCE-76 questionnaire. Seizure frequency evolution was analyzed as a secondary endpoint.Results: Mean age was 9.7 ± 5.0 years; 63% were male. Lennox-Gastaut syndrome and related conditions accounted for 75% of the cohort. The global QOLCE score improved significantly after CBD treatment (129 ± 69.2 vs. 149 ± 82.3; p < 0.01, mean Δ = +19.7). Significant improvements were observed in behavior (p = 0.014), well-being (p = 0.016), cognition (p < 0.01), physical activities (p = 0.039), and social interactions (p = 0.02). A ≥50% seizure reduction was achieved in 63% of patients (19/30) at a mean dose of 16 mg/kg/day, with good tolerability and no serious adverse events.Significance: CBD treatment was associated with statistically and clinically significant QoL improvement across multiple domains in children with drug-resistant epilepsy. Seizure frequency reduction was observed in the majority of patients. These findings support earlier consideration of CBD in complex pediatric epilepsies and highlight the need for prospective, randomized controlled trials to confirm these results.

An efficient nitrate uptake system contributes to the improvement of crop nitrogen use efficiency under low nitrogen availability. The High Affinity nitrate Transport System (HATS) in plants is active in low range of external nitrate and is mediated by a two-component system (high affinity transporters NRT2 associated to a partner protein NRT3 (NAR2)). In Brachypodium, the model plant for C3 cereals, we investigated the role of BdNRT2A and BdNRT3.2 through various experimental approaches. Expression profile of BdNRT2.A and BdNRT3.2 genes in response to nitrate availability fits perfectly with the characteristics of the HATS components. 15Nitrate influx measurements decreased in bdnrt2a mutants (one NaN3 induced mutant with a truncated NRT2A protein and two amiRNA mutants). In addition, the N limited phenotype of the mutant with a truncated NRT2A protein confirmed that BdNRT2A is a major contributor of the HATS in Brachypodium. An effective nitrate transport in the heterologous expression system Xenopus oocytes required the coexpression of BdNRT2A and BdNRT3.2 that characterizes two-component system of the HATS. Functional interaction between BdNRT2A-GFP and BdNRT3.2-RFP fusion proteins was observed at the plasma membrane in Arabidopsis protoplasts in transient expression experiments with BdNRT3.2 being necessary for the plasma membrane localization of BdNRT2A. The role of a conserved Ser residue in BdNRT2A (S461) specific to monocotyledons was evaluated in the BdNRT2A and BdNRT3.2 interaction leading to plasma membrane targeting. Assuming that S461 could be regulated by phosphorylation, a directed mutagenesis was performed to mimic a nonphosphorylated (S461A) or a constitutively phosphorylated (S461D), However, the mimicking the phosphorylation status of S461 by mutagenesis did not modify the BdNRT2A and BdNRT3.2 interaction, suggesting a more complex regulating mechanism. In conclusion, our data show that BdNRT2A and BdNRT3.2 are the main components of the nitrate HATS activity in Brachypodium (Bd21-3) and allow an optimal growth in low N conditions.

HHV-6 meningoencephalitis has been reported in immunocompromised individuals but is very uncommon in immunocompetent individuals. However, HHV-6 is the second most frequently detected virus in multiplex PCR tests. As HHV-6 DNA integrates in the telomeric region of host chromosomes after primary infection and can be passed onto offspring, 1 % of the population carries an inherited HHV-6 genome (iciHHV-6). This makes it difficult to interpret a positive multiplex PCR test for HHV-6. Here, we describe a 39-year-old female patient with an unremarkable medical history and who was hospitalized for meningoencephalitis. The brain imaging findings were normal. The positive multiplex PCR test for HHV-6 was confirmed by qualitative and quantitative HHV-6 PCR tests, the viral load was higher in blood than in CSF. The presence of circulating anti-CMV IgM and IgG in a serologic test and the absence of other pathogens argued in favor of a primary CMV infection. However CMV PCR was negative. The chromosomal integration of HHV-6 was subsequently confirmed by the results of a hair bulb analysis. Our primary hypothesis was CMV meningoencephalitis in a context of inherited chromosomic integration of HHV-6 without be able to confirm the possible role of HHV-6 (reactivation or bystander) in this situation. A commercially available assay able to certify HHV-6 replication in a context of iciHHV-6 would have been useful to conclude.

Nitrogen nutrition is essential for crop yield, but applying fertilizers has detrimental effects on the environment. Compartmenting nitrate into vacuoles is one of the options to develop nitrogen-efficient crops adapted to less fertilizers. Only a few proteins involved in nitrate transport in the tonoplast have been identified. CLCa is the major transporter involved in nitrate storage in Arabidopsis, but it can also facilitate nitrate remobilization from the vacuole in guard cells. Several other nitrate transporters, including NRT2.7, have been localized in this membrane. The transport mechanism of NRT2.7 has not yet been defined as this protein is present mainly in seed cells that are not easily amenable to electrophysiology analysis. Here, we investigated NRT2.7 function through its ectopic overexpression in a clca knockout mutant. Although the decrease in growth of clca on nitrogen-sufficient medium was complemented, nitrate homeostasis was not restored by NRT2.7 activity. Moreover, NRT2.7 ectopic overexpression in the wild-type background increased growth under limiting nitrogen supply, suggesting that NRT2.7 stimulates nitrate efflux from vacuoles. This hypothesis was demonstrated by electrophysiological nitrate flux measurements on isolated vacuoles. This discovery of NRT2.7 function, and more particularly the coupling of vacuolar nitrate fluxes with growth under low nitrate supply, will enable new strategies for engineering better NUE for a more sustainable agriculture.

INTRODUCTION:Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurological disease usually described in adults. Expanded CAG repeats in the ATXN2 gene can lead to pediatric onset. This study aims to describe the natural history of SCA2 in children. METHODS:We analyzed clinical and genetic data from 22 children with SCA2 across 17 institutions and compared them to 20 previously reported cases. RESULTS:The phenotype of pediatric SCA2 can be divided into two distinct groups based on CAG repeat size and age. In the infantile group (n = 9), developmental delay and seizures were prominent features, along with cerebellar and cerebral atrophy. In the juvenile group (n = 13), the disease was a cerebellar degeneration similar to adults. A threshold of 88 ± 4 CAG repeats distinguished the infantile group from the juvenile group. Pediatric SCA2 type was independent of parental origin; SCA2 was maternally inherited in 22%, including three infantile presentations. DISCUSSION:This large cohort of pediatric SCA2 disease provides the first comprehensive description of its characteristics, which differ from those of SCA7. Indeed, the phenotypic spectrum of SCA7 in children is continuous, while that of SCA2 is bimodal. Although pediatric SCA2 can be difficult to diagnose by genome-wide sequencing, it is a recognizable disease that can be easily diagnosed with a targeted study of the number of CAGs in ATXN2. Genetic counseling for families should consider the significant proportion of maternal transmission.

The annual incidence of physical child abuse is 4% to 20%. Notification of suspected child abuse to the authorities is a public health issue. The main objective was to identify the clinical signs and paraclinical factors that prompted physicians to notify the authorities of suspected child abuse. This is a retrospective cohort study at the Amiens University Hospital. We included suspected victims of child abuse under the age of 3 admitted to a pediatric unit between 01/12/2013 and 01/04/2019. Clinical data and imaging findings were retrospectively collected from the medical records and then univariate analyses were performed. We included 126 children with a mean age of 7.7 months (0.4-33 months). Notification was more likely when the child presented with neurological signs (OR [95%CI] 5.5 [1.3-23.4]) and orthopedic symptoms (OR [95%CI]: 6.0 [1.0-35.4]). With regard to imaging data, suggestive findings in cMRI (OR [95%CI]: 7.3 [3.2-16.7]), bone scintigraphy (OR [95%CI]: 11.0 [1.3-90.2]) and fundus examination (OR [95%CI]: 9.1 [2.5-33.3]) were significantly associated with the notification of suspected child abuse. Compared to the highly trained units, basic trained units had an increased risk to break the guidelines with no cMRI (OR: 10.0 95%CI [3.8-26.3]), no skeletal survey (OR: 19.0 95%CI [6.0-60.6]), no bone scintigraphy (OR: 24.6 95%CI [8.5-70.8]), no fundus (OR: 13.6 95%CI [5.1-35.8]) and no social assessment (OR: 9.9 95%CI [4.1-24.1]). Child abuse is a difficult diagnosis and its management requires advanced medical knowledge and skills. The use of complementary examinations is essential to the diagnosis and requires specialized team works. It would seem interesting to set up a medico -social protocol containing the national guidelines. However, we must not forget that some non-specific clinical signs can in certain cases be linked to abuse. (c) 2024 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.

La maltraitance physique concerne 4 % à 20 % des enfants par an. Il existe un défaut diagnostic des situations de maltraitance. L’objectif principal était de déterminer l’influence de facteurs cliniques et paracliniques dans la prise en charge de l’enfant maltraité. Il s’agit d’une étude rétrospective sur le CHU d’Amiens des patients de moins de 3ans suspects de maltraitance, hospitalisés entre le 01/12/2013 et le 01/04/2019. Les données cliniques et paracliniques ont été recueillies dans le dossier médical. Nous avons inclus 126 enfants avec un âge moyen 7,7 mois (0,4–33 mois). Une symptomatologie neurologique (OR IC95 % : 5,5 [1,3–23,4]) ou orthopédique (OR IC95 % : 6,0 [1,0–35,4]) étaient significativement liées à la réalisation d’un signalement. Un résultat compatible avec des lésions de maltraitance à l’IRMc (OR IC95 % : 7,3 [3,2–16,7]), à la scintigraphie osseuse (OR IC95 % : 11,0 [1,3–90,2]) et au fond d’œil (OR IC95 % : 9,1 [2,5–33,3]) était significativement lié à la réalisation d’un signalement. La prise en charge par des services peu qualifiés dans la prise en charge des situations de maltraitance est un facteur de risque de non réalisation des examens complémentaires adéquats nécessaires au diagnostic. La maltraitance infantile est un diagnostic difficile et sa prise en charge fait appel à des connaissances et des compétences médicales spécialisées. Le recours aux différents examens complémentaires est essentiel au diagnostic et fait appels à un travail en équipe spécialisée. Cependant, il ne faut pas oublier que certains signes cliniques non spécifiques peuvent dans certains cas être liés à une maltraitance.

IntroductionThere are no published data on the written language skills of gifted children (GC). The objective of the present study was to evaluate reading abilities of GC vs. normative data from typically developing French children (TDC). Like English, French is considered to be an opaque language.MethodGC completed the Wechsler Intelligence Scales and a battery of language tests. Only children with a score two standard deviations (SD) above the norm were included. GC with current or past academic difficulties or specific learning disorders were excluded. The GC’s scores were compared with TDC’s normative scores for language tests in a chi-square-test and corrected for multiple comparisons.ResultsForty-five GC were included. The highest GC’s mean scores were for the WISC’s Verbal Comprehension Index (VCI) and the lowest for the Processing Speed Index (from more than two SDs to one SD higher above the TDC’s normative scores). GC were between 1.3 and 4.7 times more likely than TDC to achieve a high score. After correction, the distributions of the GC’s and TDC’s scores differed significantly with regard to spoonerism, phoneme deletion, and rapid automatic naming (p < 0.001), word and sentence repetition (p ≤ 0.007), and the reading of meaningful text (p = 0.03). GC and TDC did not differ significantly for reading meaningless texts and spelling accuracy.DiscussionAs described in the literature, the GC in the present study had heterogeneous scores on the Wechsler Intelligence Scales. The GC performed better than TDC in assessments of the underlying skills of reading and when reading of meaningful texts. This advantage was lost in the absence of context, as shown by the lack of significant GC vs. TDC differences for reading meaningless texts and for spelling accuracy. Hence, GC presented a heterogeneous profile with regard to the underlying skills of reading and reading abilities. The present data should help to improve our understanding of GC’s reading skills. In particular, it is now essential to determine which written language tests and which score thresholds are appropriate for identifying specific learning disorders in GC.

PurposeAttentional and executive dysfunctions are the most frequent cognitive disorders in neurofibromatosis type 1 (NF1), with a high prevalence of attention deficit-hyperactivity disorder (ADHD). We (i) compared attentional profiles between NF1 children with and without ADHD and children with primary ADHD criteria and (ii) investigated the possible relationship between attentional disorders and "unidentified bright objects" (UBOs) in NF1.MethodsThis retrospective study included 47 NF1 children, 25 with ADHD criteria (NF1+adhd group), matched for age, sex, and cognitive level with 47 children with primary ADHD (ADHD group). We collected computer task (sustained-attention, visuomotor-decision, inhibition, and cognitive-flexibility tasks) scores normalized for age and sex, and brain magnetic resonance imaging data.Results(i) Working memory was impaired in all groups. (ii) Omissions (p<0.002) and response-time variability (p<0.05) in sustained-attention and visuomotor-decision tasks and errors (p<0.02) in the cognitive-flexibility task were lower for the NFI+adhd and ADHD groups than for the NF1-no-adhd group. (iii) The NF1+adhd group had slower response times (p<0.02) for inhibition and visuomotor-decision tasks than the other groups. (iv) We found no relevant association between cognitive performance and UBOs.ConclusionsNF1 children with ADHD have an attentional and executive functions deficit profile similar to that of children with primary ADHD, but with a slower response-time, increasing learning difficulties. The atypical connectivity of fronto-striatal pathways, poorer dopamine homeostasis, and increased GABA inhibition observed in NF1 renders vulnerable the development of the widely distributed neural networks that support attentional, working-memory, and executive functions.

Abstract Background Attention‐deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n‐3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy‐associated ADHD. Methods A multicenter double blind randomized placebo‐controlled trial evaluating supplementation with PUFA, in eicosapentaenoic‐ and docosahexaenoic‐acid form, conjugated to a phospholipid vector (PS‐Omega3) in children aged >6 and <16‐years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM‐V. After a 4‐week baseline period, patients were allocated (1:1) either to placebo group or to PS‐Omega 3 group and entered a 12 week‐double‐blind treatment period which was followed by a 12 week‐open‐label treatment period. The primary outcome was the reduction of the ADHD‐rating scale IV attention‐deficit subscore after 12 weeks of treatment. Results The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy‐four patients were randomized, 44 in PS‐Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD‐IV scale was −1.57 in the PS‐Omega3 group, and −2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD‐related secondary outcomes, with no difference between placebo and PS‐Omega3. Conclusion Our study remaining underpowered, no formal conclusion about the effect of Ps‐Omega3 could be drawn. However, our data strongly suggested that the PS‐Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy. Plain Language Summary Supplementation with polyunsaturated n‐3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo‐controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.

Even for easy-to-transform species or genotypes, the creation of transgenic or edited plant lines remains a significant bottleneck. Thus, any technical advance that accelerates the regeneration and transformation process is welcome. So far, methods to produce Brachypodium distachyon (Bd) transgenics span at least 14 weeks from the start of tissue culture to the recovery of regenerated plantlets. We have previously shown that embryogenic somatic tissues grow in the scutellum of immature zygotic Bd embryos within 3 days of in vitro induction with exogenous auxin and that the development of secondary embryos can be initiated immediately thereafter. Here, we further demonstrate that such pluripotent reactive tissues can be genetically transformed with Agrobacterium tumefaciens right after the onset of somatic embryogenesis. In brief, immature zygotic embryos are induced for callogenesis for one week, co-cultured with Agrobacterium for three days, then incubated on callogenesis selective medium for three weeks, and finally transferred on selective regeneration medium for up to three weeks to obtain plantlets ready for rooting. This 7-to-8-week procedure requires only three subcultures. Its validation includes the molecular and phenotype characterization of Bd lines carrying transgenic cassettes and novel CRISPR/Cas9-generated mutations in two independent loci coding for nitrate reductase enzymes (BdNR1 and BdNR2). With a short callogenesis stage and streamlined in vitro regeneration following co-cultivation with Agrobacterium, transgenic and edited T0 Bd plantlets can be produced in about 8 weeks, a gain of one to two months compared to previously published methods, with no reduction in transformation efficiency and at lower costs.

PURPOSE:This retrospective chart review study (GWEP20052) evaluated plant-derived highly purified cannabidiol (CBD; Epidyolex®; 100 mg/mL oral solution) use without clobazam as add-on therapy in patients aged ≥2 years with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) enrolled in a European Early Access Program. METHODS:Data were extracted from patient charts covering a period starting 3 months before CBD treatment and concluding after 12 months of CBD treatment, or sooner if a patient discontinued CBD or started clobazam. RESULTS:Of 114 enrolled patients, data were available for 107 (92 LGS, 15 DS) who received CBD without clobazam for ≥3 months. Mean age: 14.5 (LGS) and 10.5 (DS) years; female: 44% (LGS) and 67% (DS). Mean time-averaged CBD dose: 13.54 (LGS) and 11.56 (DS) mg/kg/day. Median change from baseline in seizure frequency per 28 days over 3-month intervals varied from -6.2% to -20.9% for LGS and 0% to -16.7% for DS. Achievement of ≥50% reduction in drop (LGS) or convulsive (DS) seizures at 3 and 12 months: LGS, 19% (n = 69) and 30% (n = 53); DS, 21% (n = 14) and 13% (n = 8). Retention on CBD without clobazam (enrolled set): 94%, 80%, 69%, and 63% at 3, 6, 9, and 12 months. Adverse event (AE) incidence was 31%, most commonly somnolence, seizure, diarrhea, and decreased appetite. Two patients discontinued CBD owing to AEs, and four patients with LGS experienced elevated liver enzymes. CONCLUSION:Results support favorable effectiveness and retention of CBD without concomitant clobazam for up to 12 months in clinical practice.

Sensory processing difficulties are worth exploring in youths with ASD and feeding problems considering their high frequency and therapeutic potential. To synthesize prior knowledge and discrepancies between studies, a systematic review and meta-analysis were conducted. The quality of the 16 reviewed studies was regarded as moderate. The association between sensory processing difficulties in all modalities and problematic eating behaviors was not statistically significant. Oral sensory processing difficulties were associated with food refusal (SMD = − 0.88, p = 0.04) and all types of problematic eating behavior (SMD = − 1.31, p < .001), with little evidence supporting the role of atypical sensory processing in non-oral modalities. These findings highlight the importance of considering oral sensory processing performance of youths with ASD and eating complaints.

PurposeIn this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes,CC2D2A.MethodsWe selected 53 patients with pathogenic variants onCC2D2A, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature.ResultsDevelopmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype–phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype.ConclusionThis study contradicts previous literature stating an association betweenCC2D2A-related JS and ventriculomegaly. Our study implies thatCC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.

Aim KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants. Methods We included 25 patients with a KCNB1 encephalopathy, aged from 3.2 to 34.1 years (median = 10 years). Adaptive functioning was assessed in all patients using the French version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaire. We screened global behavior with the Childhood Behavioral Check-List (CBCL, Achenbach) and autism spectrum disorder (ASD) with the Social Communication Questionnaire (SCQ). We used a cluster analysis to identify subgroups of adaptive profiles. Results VABS-II questionnaire showed pathological adaptive behavior in all participants with a severity of adaptive deficiency ranging from mild in 8/20 to severe in 7/20. Eight out of 16 were at risk of Attention Problems at the CBCL and 13/18 were at risk of autism spectrum disorder (ASD). The adaptive behavior composite score significantly decreased with age (Spearman's Rho=-0.72, p<0.001) but not the equivalent ages, suggesting stagnation and slowing but no regression over time. The clustering analysis identified two subgroups of patients, one showing more severe adaptive behavior. The severity of the epilepsy phenotype predicted the severity of the behavioral profile with a sensitivity of 70% and a specificity of 90.9%. Conclusion This study confirms the deleterious consequences of early-onset epilepsy in addition to the impact of the gene dysfunction in patients with KCNB1 encephalopathy. ASD and attention disorders are frequent. Parental questionnaires should be considered as useful tools for early screening and care adaptation.

Background: Overall and respiratory management of preterm children are constantly evolving, which might have changed both the pathophysiology and neurodevelopmental consequences of bronchopulmonary dysplasia (BPD). Objectives: The objective of this study is to determine whether the previously shown association between BPD and risk of developmental delay persists. Methods: The study population was children born before 32 weeks’ gestation from the French prospective cohort EPIPAGE-2. The exposure was BPD assessed at 36 weeks’ postmenstrual age. The main outcome was risk of developmental delay defined by an Age & Stages Questionnaires (ASQ) score below threshold at 24 months’ corrected age. Results: The analyzed population included 2,706 children. Among those with available ASQ score, 196/1,587 had BPD and 671/1,587 had an ASQ score below threshold. BPD was associated with an ASQ score below threshold (odds ratio 1.52, 95% confidence interval 1.11–2.08; p = 0.008). Conclusions: BPD was strongly associated with risk of developmental delay.

We report on a 7-year-old female who presented paroxysmal episodes of loss of consciousness with clonic movements. The electroencephalogram (EEG) evidenced diffuse slow wave activations, with no symptoms. Epilepsy was suspected but antiepileptic drugs were ineffective. Video-EEG monitoring revealed that the syncope was triggered by stretching with a tachycardia that started during the stretch maneuver and diffuse slow waves on the EEG 2s before the symptoms. Stretch syncope can result in striking manifestations with subcortically driven clonic movements that can be mistaken for signs of epilepsy. Stretching might lead to transient hypoxia of the brainstem; in turn, this might activate the thalamocortical loop and thus generate cardiovascular changes, EEG slow waves, and physical manifestations.

Objective We aimed to delineate the phenotypic spectrum and long-term outcome of individuals withKCNB1encephalopathy. Methods We collected genetic, clinical, electroencephalographic, and imaging data of individuals withKCNB1pathogenic variants recruited through an international collaboration, with the support of the family association "KCNB1 France." Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the long-term outcome in patients older than 12 years from our series and from literature. Results Our series included 36 patients (21 males, median age = 10 years, range = 1.6 months-34 years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10 months, range = 10 days-3.5 years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5 years, range = 18 months-25 years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals withKCNB1pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n = 41/61) and autistic features in 56% (n = 32/57). Long-term outcome in 22 individuals older than 12 years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. Significance Our study describes the phenotypic spectrum ofKCNB1encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechanisms should facilitate the development of targeted therapies, much needed to improve the neurodevelopmental prognosis.