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Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as “West syndrome”, new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants . The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.

Background/Objectives: Metabolic bone disease of prematurity (MBDP) is a multifactorial disorder resulting from disrupted transplacental mineral transfer and postnatal nutritional deficits, particularly affecting preterm neonates born before 32 weeks of gestation or weighing under 1500 g. Although substantial research has focused on skeletal outcomes, few studies have explored the association between MBDP and neonatal neurological impairment. This narrative review is the first to integrate the pathophysiological mechanisms, diagnostic methods, and preventive strategies for MBDP, while simultaneously investigating its potential impact on neurodevelopment. Methods: A narrative review of recent peer-reviewed studies, systematic reviews, and clinical trials was performed focusing on biochemical markers (alkaline phosphatase, FGF23, calcium, and phosphorus), emerging tools such as bioelectrical impedance analysis (BIA), and the effects of early nutritional interventions on both skeletal and neurodevelopmental outcomes in preterm infants (n = seven included articles). Results: Early elevations in ALP, particularly when combined with low serum phosphorus and FGF23 levels, provide sensitive markers for identifying MBDP. Furthermore, insufficient vitamin D levels during gestation and in the neonatal period have been associated with increased risks of seizures, hypotonia, and developmental delays. Studies suggest that enhanced vitamin D supplementation in preterm infants (up to 800 IU/day) may improve mineral absorption and bone formation and confer neuroprotective benefits through anti-inflammatory and antioxidant mechanisms. Conclusions: This is the first review on the neurological implications of biochemical actors of MBDP. As a result, diagnostic and therapeutic strategies, including vitamin D supplementation, can improve bone and neurodevelopmental outcomes. Future prospective studies are required to standardize diagnostic criteria and optimize therapeutic regimens for enhanced long-term benefits.

Background John M. Opitz, a towering figure in both stature and scientific achievement, left an indelible mark on the fields of genetics, pediatrics, and embryology. Born in 1935 in Hamburg to a Jewish family, Opitz’s early life was marked by adversities. Despite these challenges, he pursued a remarkable career, immigrating to the United States at 15 years and becoming a renowned scientist in institutions like Iowa State University and the University of Wisconsin, where he made groundbreaking contributions to clinical genetics. Main body A testament to his compassionate nature, Opitz dedicated himself to understanding and treating rare genetic disorders, earning him eponymous recognition in several medical conditions. His impact extended beyond academia, as evidenced by his collaborative efforts with Sicilian universities to advance clinical genetics in Italy. Opitz’s teaching style emphasized simplicity, empathy, and meticulous clinical examination, leaving an indelible mark on students and colleagues. Conclusion John M. Opitz’s towering intellect, compassionate demeanor, and profound impact on medicine and genetics made him a figure of enduring significance. His legacy lives on through the countless lives he touched, the knowledge he transmitted, and the enduring friendships he forged. In remembering John Opitz, we honor not only a man, but also a myth—a symbol of resilience, humanity, and scientific excellence.

Peripheral nerve sheath tumors encompass a wide spectrum of lesions with different biological behavior, including both benign and malignant neoplasms as well as the recent diagnostic category, i.e., “atypical neurofibromatous neoplasm with uncertain biologic potential” to be used only for NF1 patients. Neurofibromas and schwannomas are benign Schwann-cell-derived peripheral nerve sheath tumors arising as isolated lesions or within the context of classical neurofibromatosis or schwannomatoses. Multiple tumors are a hallmark of neurofibromatosis type 1(NF1) and related forms, NF2-related-schwannomatosis (formerly NF2) or SMARCB1/LZTR1-related schwannomatoses. Perineuriomas are benign, mostly sporadic, peripheral nerve sheath tumors that show morphological, immunohistochemical, and ultrastructural features reminiscent of perineurial differentiation. Hybrid tumors exist, with the most common lesions represented by a variable mixture of neurofibromas, schwannomas, and perineuriomas. Conversely, malignant peripheral nerve sheath tumors are soft tissue sarcomas that may arise from a peripheral nerve or a pre-existing neurofibroma, and in about 50% of cases, these tumors are associated with NF1. The present review emphasizes the main clinicopathologic features of each pathological entity, focusing on the diagnostic clues and unusual morphological variants.

Vitamin K prophylaxis represents a paradigmatic example of how molecular mechanisms directly translate into effective neonatal preventive care. In newborns, physiological immaturity of vitamin K metabolism, including limited placental transfer, low hepatic reserves, immature intestinal absorption, and dependence on vitamin K-dependent γ-carboxylation pathways, creates a unique vulnerability to vitamin K deficiency bleeding (VKDB). This narrative review integrates molecular and biochemical mechanisms with neonatal physiology and clinical evidence to examine the effectiveness of current prophylactic strategies. At the molecular and pharmacokinetic level, intramuscular (IM) administration ensures sustained bioavailability and reliable activation of vitamin K-dependent proteins, whereas oral regimens are more sensitive to formulation, dosing schedules, and absorption efficiency. Consistently, clinical and surveillance data demonstrate near-complete protection against both classic and late VKDB following IM prophylaxis, while oral approaches show greater variability, particularly in real-world settings. Importantly, increasing parental refusal of IM vitamin K undermines an intervention with well-established molecular efficacy, contributing to preventable severe bleeding events. By linking mechanistic foundations to clinical outcomes and implementation challenges, this review provides a translational framework for clinicians, researchers, and policymakers aiming to optimize neonatal vitamin K prophylaxis in contemporary practice.

Background The diagnosis of mitochondrial disorders (MDs) in pediatric patients is complex and often delayed due to heterogeneous clinical presentations and limited access to invasive confirmation tests such as muscle biopsy. Objective To evaluate the diagnostic sensitivity and specificity of a targeted next-generation sequencing (NGS) panel (Blueprint Genetics ® “FLEX Comprehensive Epilepsy Panel Plus”) for detecting MDs in a cohort of pediatric patients with neurological symptoms compared with gold standard tissue biopsy and clinical follow-up. The primary endpoint was the diagnostic accuracy of targeted NGS panel testing for pediatric MDs. The secondary endpoints were the identification of clinical predictors and biochemical correlations associated with increased diagnostic yield and the assessment of age-dependent diagnostic patterns. Methods We enrolled 36 pediatric patients between May 2022 and July 2023 on the basis of predefined clinical criteria suggestive of MDs. All patients underwent buccal swab-based targeted NGS testing. Confirmatory tissue biopsies and functional studies were performed in selected cases as the gold standard reference. True positives were defined as pathogenic/likely pathogenic variants confirmed by tissue biopsy and/or strong clinical correlation. Statistical analyses included Pearson correlation, Fisher’s exact test, and univariate logistic regression, stratifying data by age of onset and clinical features. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure methodological rigor and transparency. This was a convenience sample without a priori power calculation. Results Five patients (5/34 out of 36 patients who completed the study, 14.7%) harbored variants in MD-associated genes. Pathogenic or likely pathogenic variants were confirmed in three cases through tissue biopsy, acting as true positives. The sensitivity was 100% (95% CI: 29.2–100%), the specificity was 94% (95% CI: 79.6–99.3%), the accuracy was 94% (95% CI: 80.3–99.3%), and the positive predictive value was 60% (95% CI: 14.7–94.7%). The positive predictive value reflects the presence of variants of uncertain significance (VUS) requiring further validation. Statistically significant correlations were observed between the presence of MD variants and elevated blood lactate ( R  = 0.51, p  < 0.05) and GGT levels ( R  = 0.46, p  < 0.05) and reduced hemoglobin ( R =-0.42, p  < 0.05). Eight specific clinical signs, occurring at < 12 months of age, strongly predicted MD-related variants with statistical significance ( p  < 0.05). Conclusion Targeted NGS via buccal swabs demonstrates high accuracy and specificity in diagnosing pediatric MDs when guided by a structured clinical phenotype and confirmed by tissue analysis. Early onset of specific clinical signs should prompt NGS testing and may reduce unnecessary invasive procedures. Early diagnosis enables improved patient management and family counseling.

Background Wilson disease (WD) is an Autosomal-Recessive disorder due to mutations of ATP7B gene on chromosome 13q14.3 . Inadequate protein function leads to low ceruloplasmin blood levels and copper accumulation in liver, basal ganglia and chornea. Main clinical manifestations are hypertransaminasemia, tremors, dysarthria, dystonia and psychiatric symptoms. The phenotypic variability in WD is considerable and its onset can be heterogeneous: the most common type in childhood is the hepatic involvement, followed by the neurological one or others. The presence of a genotype-phenotype correlation has not yet been fully demonstrated. The phenotypic variability may be explained by the intervention of other modifier genes regulating copper metabolism in the presence of mutations ATP7B. Case presentation A streaking phenotypic variability was observed in two Sicilian sisters carrying the same genotype for ATB7B gene [ c.3207C > A / c. 3904-2A > G ]. Although both started to present signs at age 10 years, onset was characterized by neurological signs in the first (tremors, motor incoordination, language and cognitive impairment), while liver involvement has been the only sign in the other. They started the same chelation therapy. After a 20-year follow-up the former is severely affected (MRI evidence of basal ganglia copper deposits and hyperchogenic liver, thrombocytopenia), while the latter presents only a moderate liver enlargement. In literature, the splice mutation c. 3904-2A > G is also reported in Egypt population, associated with acute liver failure or chronic hepatic disease, and it could be typical of Mediterranean area, not being reported in other geographical zones. Conclusion Based on our clinical experience in Eastern Sicily, there is a considerable phenotypic variability in WD, even in the presence of an identical genotype. The mutation c. 3904-2A > G could be associated with this phenotypic variability in Mediterranean population, but further studies should be conducted. This condition could be explained by the intervention of modifier genes regulating copper metabolism in the presence of defective ATP7B protein function. Further investigations on their role by Next Generation Sequencing or Whole Exome Analysis might have a profound impact on patients’ management and in particular on therapy.

Background and Objectives: Zinc finger proteins are important transcription factors that regulate gene expression and play a critical role in neurodevelopment including autism spectrum disorders (ASDs). They are involved in a variety of cellular processes, including cell proliferation, differentiation, and apoptosis. Materials and Methods: Whole-exome sequencing (WES) analysis on a patient diagnosed with ASD. Results: Sequencing identified a homozygous insertion causing a stop codon, resulting in the removal of several functional domains including the zinc finger C2HC/C3H type of the ZC2HC1C protein. To date, no MIM entry has been assigned to the detected gene. In silico predictions described the variant as likely pathogenic, indicating an autosomal recessive inheritance pattern. In this study, we hypothesize that this homozygous mutation disrupts protein function and may represent a susceptibility gene for autism. The parents and the patient’s sister were healthy and carry the variant in the heterozygous condition. This gene is expressed in brain tissues showing high expression in both the choroid plexus (ChP) and midbrain, whose dysfunctions, as reported, may lead to ASD. Moreover, predictive pathway analyses indicated the probable involvement of this gene in primary cilia development. This process has been frequently linked to neurodevelopmental impairments, such as autism, as documented in previous studies. Conclusions: Further analyses are needed via in vitro functional assays or by ZC2HC1C gene knockout to validate its functional role.