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Background/Objectives: Digital technologies have become increasingly integrated into the daily lives of children and adolescents, largely because their interactive and visually engaging design is particularly suited to the younger users. The COVID-19 pandemic further accelerated this trend, significantly lowering the average age of access to the digital devices. However, scientific consensus remains divided regarding the developmental impact of digital media use—particularly its cognitive, motor, and emotional consequences—depending on whether the use is passive or active. This review aims to explore these effects across developmental stages, focusing on both behavioral and neurobiological dimensions, and to identify emerging risks and protective factors associated with digital engagement. Methods: A PRISMA review was conducted on the impact of digital media use among pre-school children and adolescents. Behavioral, psychosocial, and neurobiological aspects were examined, with specific attention to epigenetic changes, techno-stress, digital overstimulation, and immersive technologies (e.g., virtual and augmented reality). Results: The findings suggest that passive digital consumption is more often associated with negative outcomes, such as impaired attention and emotional regulation, especially in younger children. Active and guided use may offer cognitive benefits. Neurobiological research indicates that chronic exposure to digital stimuli may affect stress regulation and neural development, possibly via epigenetic mechanisms. Effects vary across developmental stages and individual vulnerabilities. Conclusions: A nuanced understanding of digital engagement is essential. While certain technologies can support development, excessive or unguided use may pose risks. This review provides age-specific recommendations to foster balanced and healthy technology use in children and adolescents.

Background/Objectives: Cutaneous hypopigmentation is a common clinical sign observed in a variety of disorders. It may be congenital or acquired, localized or diffuse, and can range from benign to being associated with systemic conditions, including those affecting the central nervous system. Recognition of the key clinical features associated with each disorder is essential for accurate diagnosis and for differentiating one condition from another. Methods: PubMed, Embase, and Scopus databases were used to prepare a systematic review. Search terms were: “congenital”, “cutaneous”, “localized”, “diffuse”, “hypopigmentation” and “neurological disorders/signs”. The focus was on congenital cutaneous hypopigmentation, distinguishing between localized and diffuse presentations, with emphasis on neurological involvement. Peer-reviewed articles, case series, and original studies with neurological manifestations of the disease were reviewed. Cutaneous hypopigmentation disorders associated with diffuse cerebral involvement include syndromes such as Chediak–Higashi, Griscelli, Elejalde, Cross, Tietz albinism-deafness, Prader–Willi, Angelman, and several congenital metabolic disorders. In contrast, the ‘localized’ group comprises syndromes such as Waardenburg, Incontinentia pigmenti, and the phacomatoses, including hypomelanosis of Ito and tuberous sclerosis complex. Results: Overlapping phenotypes and genetic heterogeneity lead to diagnostic challenges and potential errors suggesting multiple specialists. The main clinical features of each disorder are discussed, with particular attention paid to neurological signs. A practical flowchart is provided to help distinguish between ‘diffuse’ and ‘localized’ forms with neurological involvement. Conclusions: Early identification of cutaneous features, followed by comprehensive clinical and instrumental evaluation, enables timely and accurate diagnosis, ultimately improving the clinical outcomes for affected children.

Background/Objectives: Child abuse is a pervasive global issue with significant implications for the physical, emotional, and psychological well-being of victims. This review highlights the clinical, molecular, and therapeutic dimensions of child abuse, emphasizing its long-term impact and the need for interdisciplinary approaches. Early exposure to abuse activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to chronic cortisol release and subsequent neuroplastic changes in brain regions such as the hippocampus, amygdala, and prefrontal cortex. These molecular alterations, including epigenetic modifications and inflammatory responses, contribute to the heightened risk of psychiatric disorders and chronic illnesses in survivors. Clinically, child abuse presents with diverse manifestations ranging from physical injuries to psychological and developmental disorders, making timely diagnosis challenging. Methods: A multidisciplinary approach involving thorough clinical evaluation, detailed histories, and collaboration with child protection services is essential for accurate diagnosis and effective intervention. Results: Recent advances in molecular biology have identified biomarkers, such as stress-related hormones and epigenetic changes, which provide novel insights into the physiological impact of abuse and potential targets for therapeutic intervention. Current treatment strategies prioritize the child’s safety, psychological well-being, and prevention of further abuse. Trauma-focused cognitive behavioral therapy and family-centered interventions are pivotal in promoting recovery and resilience. Conclusions: Emerging research focuses on integrating molecular findings with clinical practice, utilizing digital health tools, and leveraging big data to develop predictive models and personalized treatments. Interdisciplinary collaboration remains crucial to translating research into policy and practice, ultimately aiming to mitigate the impact of child abuse and improve outcomes for survivors.

FIRES is defined as a disorder that requires a prior febrile infection starting between 2 weeks and 24 h before the onset of the refractory status epilepticus with or without fever at the onset of status epilepticus. The patients, previously normal, present in the acute phase recurrent seizures and status epilepticus followed by a severe course with usually persistent seizures and residual cognitive impairment. Boundary with “new onset refractory status epilepticus (NORSE) has not clearly established. Pathogenetic hypothesis includes inflammatory or autoimmune mechanism with a possible genetic predisposition for an immune response dysfunction. Various types of treatment have been proposed for the treatment of the acute phase of the disorder to block the rapid seizures evolution to status epilepticus and to treat status epilepticus itself. Prognosis is usually severe both for control of the seizures and for cognitive involvement. FIRES is an uncommon but severe disorder which must be carefully considered in the differential diagnosis with other epileptic encephalopathy.

-related disorders are uncommonly reported. The clinical features of the disorders are wide and heterogeneous mainly consisting of undistinctive facial dysmorphism, mild to severe intellectual and speech delay, epileptic seizures, and motor dysfunction. Defects in gene have been identified in cases diagnosed as Pitt-Hopkins-like-syndrome 2 (PTHLS2; OMIM#614325). Literature review of -related disorders was conducted and main clinical features of individuals affected by these disorders were analyzed. In addition, clinical features of individuals labelled with PTHSL2 diagnosis were reported. A comparison between international consensus diagnostic criteria for Pitt-Hopkins syndrome (PTHS) and twins presenting with -related disorder and followed by this institution were also presented. Our data confirmed that -related disorders mainly manifest with undistinctive dysmorphic features and neurological involvement consisting of more or less severe developmental delay/intellectual disability, autistic spectrum disorder, and epilepsy. Relationship between PTHSL2 and remains to be established. Our present analysis denoted a heterogeneous and unspecific clinical framework of the -related disorders mainly affecting the nervous system for which the clinical diagnosis remains inconclusive without the support of genetic analysis. Further contributions are necessary to better clarify the clinical assessment of PTHSL2.

Klippel–Trenaunay syndrome is an uncommon, infrequent, congenital disorder characterized by a triad of capillary malformation, varicosities, and tissue and bone hypertrophy. The presence of two of these three signs is enough to obtain the diagnosis. Capillary malformations are usually present at birth, whereas venous varicosities and limb hypertrophy become more evident later. The syndrome has usually a benign course, but serious complications involving various organs, such as gastrointestinal and genitourinary organs, as well as the central nervous system, may be observed. Recently, Klippel–Trenaunay syndrome has been included in the group of PIK3CA-related overgrowth spectrum (PROS) disorders. In terms of this disorder, new results in etiopathogenesis and in modalities of treatment have been advanced. We report here a review of the recent genetic findings, the main clinical characteristics and related severe complications, differential diagnoses with a similar disorder, and the management of patients with this complex and uncommon syndrome.

Early life stress (ELS) refers to harmful environmental events (i.e., poor maternal health, metabolic restraint, childhood trauma) occurring during the prenatal and/or postnatal period, which may cause the ‘epigenetic corruption’ of cellular and molecular signaling of mental and physical development. While the impact of ELS in a wide range of human diseases has been confirmed, the ELS susceptibility to bone diseases has been poorly explored. In this review, to understand the potential mediating pathways of ELS in bone diseases, PRISMA criteria were used to analyze different stress protocols in mammal models and the effects elicited in dams and their progeny. Data collected, despite the methodological heterogeneity, show that ELS interferes with fetal bone formation, also revealing that the stress type and affected developmental phase may influence the variety and severity of bone anomalies. Interestingly, these findings highlight the maternal and fetal ability to buffer stress, establishing a new role for the placenta in minimizing ELS perturbations. The functional link between ELS and bone impairments will boost future investigations on maternal stress transmission to the fetus and, parallelly, help the assessment of catch-up mechanisms of skeleton adaptations from the cascading ELS effects.

Child abuse is a critical social issue. The orthopedic surgeon’s role is essential in noticing signs and symptoms of physical abuse. For this reason, several authors have proposed scoring systems to identify abuse early on and reduce undiagnosed cases. The aim of this systematic review is to overview the screening tools in the literature. In 2021, three independent authors performed a systematic review of two electronic medical databases using the following inclusion criteria: physical child abuse, questionnaire, survey, score, screening tool and predictive tool. Patients who had experienced sexual abuse or emotional abuse were excluded. The risk of bias evaluation of the articles was performed according to the Newcastle–Ottawa Quality Assessment Scale Cohort Studies. Any evidence-level study reporting clinical data and dealing with a physical child abuse diagnosis tool was considered. A total of 217 articles were found. After reading the full texts and checking the reference lists, n = 12 (71,035 patients) articles were selected. A total of seven screening tools were found. However, only some of the seven diagnostic tools included demonstrated a high rate of sensitivity and specificity. The main limits of the studies were the lack of heterogeneity of evidence and samples and the lack of common assessing tools. Despite the multiplicity of questionnaires aimed at detecting validated child abuse, there was not a single worldwide questionnaire for early diagnosis. A combination of more than one test might increase the validity of the investigation.

Background Alternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability. Case presentation Clinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature. Conclusions Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.

Background Mutations in GABRB3 have been identified in subjects with different types of epilepsy and epileptic syndromes, including West syndrome (WS), Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), myoclonic‐atonic epilepsy (MAE), and others. Methods and results We herewith report on a girl affected by DS, who has been followed from infancy to the current age of 18 years. Next‐generation sequencing (NGS)‐based genetic testing for multigene analysis of neurodevelopmental disorders identified two likely de novo pathogenic mutations, a missense variant in GABRB3 gene (c.842 C>T; p.Thr281IIe) and a nonsense variant found in BBS4 gene (c.883 C>T; p.Arg295Ter). Conclusion A likely relationship between the novel GABRB3 gene variant and the clinical manifestations presented by the girl is proposed. Previously, one case of DS and two of DS‐like linked with GABRB3 mutations have been reported. To the best of our knowledge, this is the first report of DS associated with this novel variant. A literature review of clinical cases with various types of epileptic encephalopathies (EEs) related to GABRB3 mutations is reported. Our study explores a likely new gene‐phenotype relationship between a novel GABRB3 gene variant and the clinical manifestations of Dravet syndrome (DS). We, herewith, report on a long‐term follow‐up of a girl affected by DS, who harbors a novel likely pathogenic variant of GABRB3. A literature review of cases with various types of epileptic encephalopathy related to GABRB3 mutations is discussed.