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Syntaxin-binding protein 6 (STXBP6), also known as amysin, is an essential component of the SNAP receptor (SNARE) complex and plays a crucial role in neuronal vesicle trafficking. Mutations in genes encoding SNARE proteins are often associated with a broad spectrum of neurological conditions defined as "SNAREopathies", including epilepsy, intellectual disability, and neurodevelopmental disorders such as autism spectrum disorders. The present whole exome sequencing (WES) study describes, for the first time, the occurrence of developmental epileptic encephalopathy and autism spectrum disorders as a result of a de novo deletion within the STXBP6 gene. The truncated protein in the STXBP6 gene leading to a premature stop codon could negatively modulate the synaptic vesicles' exocytosis. Our research aimed to elucidate a plausible, robust correlation between STXBP6 gene deletion and the manifestation of developmental epileptic encephalopathy.

Background: The AHNAK2 gene encodes a large nucleoprotein expressed in several tissues, including brain, squamous epithelia, smooth muscle, and neuropil. Its role in calcium signaling has been suggested and to date, clear evidence about its involvement in the pathogenesis of clinical disorders is still lacking., Methods: Here, we report a female 24-year-old patient diagnosed with a cardio-facio-cutaneous-like phenotype (CFC-like), characterized by epilepsy, psychomotor development delay, atopic dermatitis, congenital heart disease, hypotonia, and facial dysmorphism, who is compound heterozygote for two missense mutations in the AHNAK2 gene detected by exome sequencing., Results: This patient had no detectable variant in any of the genes known to be associated with the cardio-facio-cutaneous syndrome. Moreover, the mode of inheritance does not appear to be autosomal dominant, as it is in typical CFC syndrome. We have performed in silico assessment of mutation severity separately for each missense mutation, but this analysis excludes a severe effect on protein function. Protein structure predictions indicate the mutations are located in flexible regions possibly involved in molecular interactions., Conclusion: We discuss an alternative interpretation on the potential involvement of the two missense mutations in the AHNAK2 gene on the expression of CFC-like phenotype in this patient based on inter-allelic complementation., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Several studies have documented learning disabilities (LDs) in subjects with epilepsy, who have been shown to be at greater risk of mild neuropsychological damage, with the consequent risk of academic failure. This retrospective study aimed to investigate the peculiarities of reading and writing disorders in subjects with idiopathic epilepsy. The reading and writing performance of 35 children affected by reading and writing disorders and idiopathic epilepsy (R/WD + E group) has been compared with the performance of 37 children with only reading and writing disorders (R/WD group). A comparison group of 22 typical developing healthy children (TDC group) was also included in the study. As expected, the TDC group reached better performances in the reading and writing tests administered. Between R/WD + E and R/WD groups, there was a substantial analogy in reading and writing disabilities. The differences between the two clinical groups concern writing ability in sentences dictation and verbal and visuospatial short-term memory in digit span and memory-for-location (MFL) tests., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

An increasing number of developmental and epileptic encephalopathies have been correlated with variants of ion channel genes, and in particular of potassium channels genes, such as KCNA1, KCNA2, KCNB1, KCNQ2, KCTD7 and KCNT1. Here we report a child with an early severe developmental and epileptic encephalopathy, spastic tetraplegia, opisthotonos attacks. The whole exome sequencing showed the de novo heterozygous variant c.1411G > C (p.Val471Leu) in the KCNC2 gene. Although this is, to our knowledge, the first case of encephalopathy associated with a KCNC2 gene variant, and further confirmatory studies are needed, previous preclinical and clinical evidence seems to suggest that KCNC2 is a new candidate epilepsy gene., Competing Interests: Declaration of competing interest There is no conflict of interest among authors., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: Cognitive abilities and executive functions in children and adolescents are important indicators of quality of life as well as academic and social achievements. Cognitive and executive functioning are often impaired in patients with epilepsy and can be exacerbated by seizures and antiseizure drugs. The aim of our observational retrospective study was to assess executive functioning in patients with pediatric epilepsy, currently taking a single antiseizure medication., Materials and Methods: Records of 172 children and adolescents aged between 6 and 18 years (mean age = 12 ± 3.4 years) with newly diagnosed epilepsy who had not yet commenced an antiepileptic treatment were included in the study. Longitudinal changes in executive functioning were assessed using the EpiTrack Junior test at baseline, before the introduction of antiepileptic monotherapy, and at 3-month, 6-month, and 9-month follow-up visits. All patients commenced a single antiepileptic treatment (levetiracetam n = 54; valproic acid n = 52; ethosuximide n = 20; oxcarbazepine n = 22; carbamazepine n = 24). Age, sex, seizure types, and seizure baseline frequency were also recorded., Results: Relative to baseline, Epitrack Junior mean scores deteriorated at the 9-month follow-up visit for patients taking valproic acid, ethosuximide, and carbamazepine, but this was only statistically significant for patients taking carbamazepine. In contrast, mean scores improved for subjects taking levetiracetam and oxcarbazepine at the 9-month follow-up visit relative to baseline, but this was only statistically significant for patients taking levetiracetam., Conclusions: Levetiracetam was the only antiseizure medication that led to slight improvements in executive functioning; whereas carbamazepine led to deteriorations in cognitive functioning. Further research using double-blinded, placebo-controlled trials are needed to confirm these results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels. Methods: 68 pediatric patients aged 6-18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF). Results: The group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only. Conclusion: Depressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management. [ABSTRACT FROM AUTHOR]

Developmental and epileptic encephalopathies (DEE) are severe neurodevelopmental disorders characterized by recurrent, usually early-onset, epileptic seizures accompanied by developmental impairment often related to both underlying genetic etiology and abnormal epileptiform activity. Today, next-generation sequencing technologies (NGS) allow us to sequence large portions of DNA quickly and with low costs. The aim of this study is to evaluate the use of whole-exome sequencing (WES) as a first-line molecular genetic test in a sample of subjects with DEEs characterized by early-onset drug-resistant epilepsies, associated with global developmental delay and/or intellectual disability (ID). We performed 82 WESs, identifying 35 pathogenic variants with a detection rate of 43%. The identified variants were highlighted on 29 different genes including, 3 new candidate genes (KCNC2, STXBP6, DHRS9) for DEEs never identified before. In total, 23 out of 35 (66%) de novo variants were identified. The most frequently identified type of inheritance was autosomal dominant de novo (60%) followed by autosomal recessive in homozygosity (17%) and heterozygosity (11%), autosomal dominant inherited from parental mosaicism (6%) and X-linked dominant de novo (6%). The most frequent mutations identified were missense (75%) followed by frameshift deletions (16%), frameshift duplications (5%), and splicing mutations (3%). Considering the results obtained in the present study we support the use of WES as a form of first-line molecular genetic testing in DEEs. [ABSTRACT FROM AUTHOR]

Background: Poor academic performance of students with epilepsy seems to be a multifactorial problem related to difficulties in reading, writing, math, and logic skills. Poor school and academic performances refer to learning problems in a specific academic area due to learning disorders and learning difficulties not excluding the ability to learn in a different manner during school and academic life. Sometimes, school, academic difficulties, and Rolandic epilepsy can coexist together, and there may be comorbidities. Consequently, the risk of impaired academic performance in people with epilepsy is high. Methods: This review analyzed the relationship between Benign Epilepsy with Centro-Temporal Spikes (BECTS) and poor school and academic performance (PSAP) in children and adolescents (aged 6 to 19), and in adults (aged 20 to no age limit). The PRISMA guideline was used to guide our review strategy. Results: This research shows that Benign Epilepsy with Centro-Temporal Spikes (BECTS) and poor school and academic performances are strongly correlated. An early onset age, as well as a long persistence of seizures, correlate more closely with PSAP. On the other hand, it appears that good pharmacological control of seizures and remission from the acute phase of the pathology support better school performance. Conclusions: This review highlights how neuropsychological aspects are also involved in patients with BECTS and PSAP, both in the greater predisposition to the establishment of other neuropsychiatric conditions and in the possibility that stigma conditions and poor academic results may have repercussions on the adaptation and functioning of these subjects. Global management of the subject with BECTS and PSAP is essential, which also pays attention to the aspects of social and scholastic inclusion, both to achieve age-appropriate educational and behavioral objectives, to give the necessary tools for the growth of the individual, and to allow a serene transition to adulthood, favoring autonomous learning and better outcomes. [ABSTRACT FROM AUTHOR]

However, subjects with epilepsy and at least a psychiatric comorbidity have a morality rate 1.4 times higher compared with people who have epilepsy without a psychiatric illness, after adjusting for age and sex [[8]]. Epilepsy is one of the most widespread chronic conditions, affecting about 50 million people worldwide. A holistic evaluation of the patient with epilepsy is particularly appropriate in the case of pre-operative diagnostic monitoring of patients with drug-resistant epilepsy candidates for surgical therapies. [Extracted from the article]

Introduction: The purpose of our study was to perform a comparative analysis of social cognition in children and adolescents with epilepsy, autism spectrum disorder (ASD), specific learning disorder (SLD) and in typical development (TD) controls. The secondary aim was to relate social cognition to some clinical and demographic characteristics. Methods: Our work is a transversal observational study. The recruits were 179 children and adolescents aged between 6 and 18 years diagnosed with epilepsy, ASD, or SLD and 32 subjects with TD. All the participants underwent neuropsychological assessment of Emotion Recognition (ER) and Theory of Mind (ToM) skills. Results: All three clinical groups performed significantly worse than controls in ER and ToM. The ASD group achieved significantly lower performance than the other groups; however, the scores of SLD and epilepsy groups were comparable. The ER performances are related to non-verbal intelligence only in the group with epilepsy. Conclusion: Children and adolescents with focal epilepsy, SLD, or ASD may present a deficit of varying extent in emotion recognition and ToM, compared with TD peers. These difficulties are more pronounced in individuals with ASD, but impairment worthy of clinical attention also emerges in individuals with SLD and epilepsy. [ABSTRACT FROM AUTHOR]

Deficits in facial emotion recognition and Theory of Mind are frequent in patients with epilepsy. Although this evidence, studies on pediatric age are few and the relation between these abilities and other cognitive domain remains to be better elucidated. The purpose of our study is to evaluate facial emotion recognition and Theory of Mind in children and adolescents with focal epilepsy, and correlate them with intelligence and executive functions. Our work is a cross-sectional observational study. Sixty-two children and adolescents aged between 7-16 years diagnosed by focal epilepsy and 32 sex/age-matched controls were recruited. All participants were administered a standardized battery tests to assess social cognition (NEPSY-II), executive functions (EpiTrack Junior) and cognitive non-verbal level (Raven Progressive Matrices). Emotion recognition mean score was significantly lower in the epilepsy group than in the controls to Student's t-test (p <0.05). Epilepsy group showed an impairment in happiness, sadness, anger and fear recognition, compared to controls (p <0.05). Theory of Mind mean score was also significantly lower in epilepsy group than controls (p <0.05). Deficits in emotion recognition seemed to be related to low age at onset of epilepsy, long duration of disease, low executive functions and low non-verbal intelligence. Deficits in Theory of Mind seemed to be related to a high seizure frequency. Our results suggest that children and adolescents with focal epilepsy had deficit in facial emotion recognition and Theory of Mind, compared to their peer. Both these difficulties seem to be related to some features of epilepsy itself. Our results also suggest that deficits in facial emotion recognition are potentially related to difficulties in executive functions and non-verbal intelligence. More studies are needed to confirm these hypotheses. • 62 children and adolescents with focal epilepsy and 32 controls were recruited. • All participants performed standardized test to assess social cognition, executive functions and cognitive non-verbal level. • Emotion recognition and Theory of Mind score was significantly lower in the epilepsy group. • Emotion recognition seemed related to age at onset and duration of epilepsy, executive functions and non-verbal intelligence. • Deficits in Theory of Mind seemed to be related to a high seizure frequency. [ABSTRACT FROM AUTHOR]

An early and effective diagnosis, as well as precision treatment, are of fundamental importance and should be pursued for improving the outcomes of these patients. Benedetto et al. evaluated the one-year diagnostic stability of autism spectrum disorder diagnosis in a clinical sample of young children who had received an early diagnosis. Neurodevelopmental disorders are a group of neuropsychiatric diseases that affect the developing brain due to a complex interaction between genetic and environmental factors. [Extracted from the article]

Sturge-Weber-Krabe syndrome (SWS), also known as encephalotrigeminalangiomatosis and named the forthfacomatosis, recall the names of the authors who first describedit in its basic clinical, radiological andanatomopathological aspects. We report here 14 cases of Sturge-Weber disease. In 6 of these, despite what had been previously described in literature, an extension of the angioma has been noted in other parts of the body. The study of these subjects stresses not only the need for a pharmacological/neuropsychomotor intervention, but alsothe need of a psychotherapeutic approach, for the emotional and affective implications thatcould derive from this syndrome. The reported cases are similar to those presented in literature for their main features. In particular, two elements are interesting: i) the exceptional diffusion of the red nevousto the whole hemicorpo; and ii) the evaluation of the way the patients live the disease, which has not beenpreviously considered in literature. We can conclude that SWS is a multisystem disorder that requires the neurologist to be aware of the possible endocrine, psychiatric, ophthalmological, and other medical issues that can arise and impact on the neurological status of the patients. [ABSTRACT FROM AUTHOR]

Introduction: Psychogenic nonepileptic seizures (PNES) are observable abrupt paroxysmal changes in behavior or consciousness that resemble epileptic seizures, but without concurrent electroencephalographic abnormalities. Methods: In this manuscript, we reviewed literature concerning pediatric PNES and focused on those articles published in the last 10 years, in order to try to understand what the state of the art is at the moment, particularly as regards relationship and differential diagnosis with epilepsy. Results: Psychogenic nonepileptic seizures have been extensively described in literature mainly in adults and less frequently in children. Despite the potential negative impact of a misdiagnosis (unnecessary investigations and antiepileptic drugs, structured pathological behavioral patterns), in literature there is little information regarding the real prevalence, clinical features, treatment, and outcome of PNES in children and adolescents. Conclusion: Psychogenic nonepileptic seizures are common but frequently missed entity in pediatric population. Diagnosis could be difficult, especially in those children who have both epileptic and nonepileptic seizures; video EEG and home video can help clinicians in diagnosis. More studies are needed to better classify PNES in children and facilitate diagnosis and treatment. [ABSTRACT FROM AUTHOR]