Whole Exome Sequencing as a First-Line Molecular Genetic Test in Developmental and Epileptic Encephalopathies.

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.

STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy.

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.

Telecoaching: a potential new training model for Charcot-Marie-Tooth patients: a systematic review.

Introduction: Charcot-Marie-Tooth disease (CMT) is an inherited neuropathy that affects the sensory and motor nerves. It can be considered the most common neuromuscular disease, with a prevalence of 1/2500. Methods: Considering the absence of a specific medical treatment and the benefits shown by physical activity in this population, a systematic review was completed using several search engines (Scopus, PubMed, and Web of Science) to analyze the use, effectiveness, and safety of a training program performed in telecoaching (TC). TC is a new training mode that uses mobile devices and digital technology to ensure remote access to training. Results: Of the 382 studies identified, only 7 met the inclusion criteria. The effects of a TC training program included improvements in strength, cardiovascular ability, and functional abilities, as well as gait and fatigue. However, the quality of the studies was moderate, the size of the participants in each study was small, and the outcome measured was partial. Discussion: Although many studies have identified statistically significant changes following the administration of the TC training protocol, further studies are needed, with appropriate study power, better quality, and a higher sample size.

Neurodevelopmental Disorders and Suicide: A Narrative Review.

Specific risk factors for self-harm and suicide in children and adolescents with neurodevelopmental disorders (NDD) may differ from those in the general population within this age range. In the present review paper, we conducted a narrative analysis of the literature, aiming to establish a connection between suicide and affective disorders in children and adolescents with NDD. Emotion dysregulation (ED) as an individual factor and adverse childhood experiences (ACE) as environmental factors are discussed as risk factors for suicidality in all individuals with NDD. We propose a theoretical model in which ED and ACE can directly lead to self-harm or suicide, directly or indirectly by interacting with depressive spectrum disorders. Additionally, we suggest that specific risk factors are more frequently associated with each of the neurodevelopmental disorders listed in the DSM-V. This review underlines the key points useful to improve the knowledge of the trajectory leading to suicide risk in NDDs with the purpose to facilitate the early identification of the suicide risk.

Comorbidities and Disease Duration in Tourette Syndrome: Impact on Cognition and Quality of Life of Children.

BACKGROUND: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. METHODS: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6-16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. RESULTS: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. CONCLUSIONS: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.

The Complex Association between Sleep Quality, Psychological Wellbeing, and Neurodevelopmental Disorders in Childhood.

During child development, the psychophysiological state is influenced by factors such as family routine, school experiences, stressful life events, or, in general, the environmental context in which the child grows up [...].

Use and Abuse of Digital Devices: Influencing Factors of Child and Adolescent Neuropsychology.

The impact of technology on human life is significant, touching various aspects such as communication, economy, education, medicine, industry, and even ecosystems [...].

Epilepsy: A Multifaced Spectrum Disorder.

Epilepsy is one of the most widespread chronic conditions, affecting about 50 million people worldwide [...].

Diet-Related Attitudes, Beliefs, and Well-Being in Adolescents with a Vegetarian Lifestyle.

Vegetarianism can meet healthy, ethical, or ecological values (such as equality and protection of animals or the environment). At the same time, it can represent a response to the need for self-determination in adolescence. Furthermore, some studies show vegetarians have greater depressive risk and a lower sense of body satisfaction. Considering the spread of non-meat diets in the Western world, researchers have investigated the benefits and risks to physical and psychological health. Despite this, few studies have been conducted on factors influencing adolescent's vegetarian diet-related attitudes. Through self-administered loosely structured interviews, this research investigated factors potentially associated with vegetarian choices in adolescence. It checked (a) gender differences in vegetarian choices; (b) religious, familial, ethical, or health factors implied in vegetarian choices; and (c) indicators of well-being among young vegetarians. The findings suggest that for our sample, non-vegetarians have lower scores on health-related questions than others, while for vegetarian adolescents, the benefits of vegetarianism mainly depend on their ethical stances, beliefs, and values. Conversely, it is unrelated to factors such as the desire to lose weight, dissatisfaction about one's body shape, or depressive feelings.

Effectiveness of an Educational Filmmaking Project in Promoting the Psychological Well-Being of Adolescents with Emotive/Behavioural Problems.

Evidence suggests that adolescents respond positively to simple, early interventions, including psychosocial support and educational interventions, even when offered in non-clinical settings. Cinematherapy can help manage life challenges, develop new skills, increase awareness, and offer new ways of thinking about specific problems. This pilot trial was conducted in Italy, aiming to investigate the effects of a six-week filmmaking course on the psychological well-being of adolescents (N = 52) with emotional/behavioural problems and neurodevelopmental disorders. At the end of the project, most participants showed improvements mostly in social skills, such as social cognition (p = 0.049), communication (p = 0.009), and motivation (p = 0.03), detected using the SRS Social Responsiveness Scale. In addition, social awareness (p = 0.001) increased in all patients. Statistically significant differences resulted in four sub-scales of Youth Self-Report Scale: withdrawn/depressed (p = 0.007), social problems (p = 0.003), thought problems (p < 0.001), and rule-breaking behaviour (p = 0.03); these results showed a decrease in emotional and behavioural problems. This study is an innovative therapeutic and educational approach based on the filmmaking art. This research can offer an empirical basis for the effectiveness of alternative therapeutic tools in child and adolescent psychiatric disorders. At the same time, it can be replicated in broader contexts (e.g., school and communities) to promote children's psychological well-being.