Background. PMP22-related neuropathies comprise a spectrum of predominantly demyelinating disorders, most commonly Charcot–Marie–Tooth type 1A (CMT1A; 17p12 duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; 17p12 deletion), with rarer phenotypes due to PMP22 sequence variants (CMT1E, Dejerine–Sottas syndrome [DSS]). Methods. We conducted a PRISMA-compliant systematic review (PROSPERO ID: 1139921) of PubMed and Scopus (January 2015–August 2025). Eligible studies reported genetically confirmed PMP22-related neuropathies with clinical and/or neurophysiological data. Owing to heterogeneous reporting, we synthesized pooled counts and proportions without meta-analysis, explicitly tracking missing denominators. Results. One hundred twenty-seven studies (n = 4493 patients) were included. Sex was available for 995 patients (males 53.8% [535/995]; females 46.2% [460/995]); mean age at onset was 23.7 years in males and 16.4 years in females. Phenotypic classification was reported for 4431/4493 (75.4% CMT1A, 20.9% HNPP, 2.6% CMT1E, 1.2% DSS). Across phenotypes, weakness/foot drop was the leading presenting symptom when considering only cohorts that explicitly reported it (e.g., 65.3% in CMT1A; 76.0% in HNPP); sensory complaints (numbness, paresthesia/dysesthesia) were variably documented. Neurophysiology consistently showed demyelinating patterns, with median and ulnar nerves most frequently abnormal among assessed nerves; in HNPP, deep peroneal and sural involvement were also common in evaluated subsets. Comorbidities clustered by phenotype: orthopedic/neuromuscular features (pes cavus/hammer toes, scoliosis/kyphosis, tremor) in CMT1A and DSS; broader metabolic/autoimmune and neurodevelopmental associations in HNPP; and higher syndromic/ocular/hearing involvement in CMT1E. Genetically, 75.6% (3241/4291) had 17p12 duplication, 19.6% (835/4291) 17p12 deletion, and 4.8% (215/4291) PMP22 sequence variants with marked allelic heterogeneity. Among 2571 cases with available methods, MLPA was most used (41.9%), followed by NGS (20.4%) and Sanger sequencing (17.8%). Main limitations include heterogeneous and incomplete reporting across studies (especially symptoms and nerve-specific data) and the absence of a formal risk-of-bias appraisal, which preclude meta-analysis and may skew phenotype proportions toward more frequently reported entities (e.g., CMT1A). Conclusions. Recent literature confirms that PMP22 copy-number variants account for the vast majority of cases, while sequence-level variants underpin a minority with distinct phenotypes (notably CMT1E/DSS). Routine MLPA, complemented by targeted/NGS, optimizes diagnostic yield. Standardized reporting of nerve-conduction parameters and symptom denominators is urgently needed to enable robust cross-study comparisons in both pediatric and adult populations.

Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance and association with comorbid conditions remain poorly understood. This study aimed to examine the prevalence of TW in a large Italian cohort of children with ASD and to explore its association with ASD severity, sleep disturbances, feeding behaviors, and gastrointestinal symptoms. Materials and Methods: A total of 289 children with ASD and 289 typically developing controls (TDC), matched for age and sex, were evaluated in a multicentric observational study. TW was assessed during neurodevelopmental evaluations. Sleep quality was assessed using the Sleep Disturbance Scale for Children (SDSC), feeding behaviors via the Brief Autism Mealtime Behavior Inventory (BAMBI), and gastrointestinal symptoms through clinical reporting. Statistical analyses included Chi-square tests, Mann–Whitney U tests, Spearman correlations, and logistic regressions. Results: TW was significantly more prevalent in the ASD group (27.3%) than in TDC (5.5%, p < 0.0001). Within the ASD group, TW occurred in 50.5% of children with Level 3 severity but was absent in Levels 1 and 2 (p < 0.0001). Males exhibited TW more frequently than females. Children with TW had higher SDSC scores (ρ = 0.33, p < 0.0001), though no subscale independently predicted TW. Constipation was reported in 100% of children with Level 3 ASD and was strongly correlated with SDSC total scores (ρ = 0.58, p < 0.0001). The Disorders of Arousal (DA) subscale emerged as an independent predictor of constipation (β = 0.184, p = 0.019). Conclusions: TW in ASD appears to be a marker of greater neurodevelopmental severity and is associated with sleep disturbances and gastrointestinal dysfunction. These findings support the hypothesis that TW may reflect broader dysfunctions involving the gut–brain axis, sensory processing, and motor control. The routine clinical assessment of TW should include the evaluation of sleep and somatic symptoms to better understand the multisystemic nature of ASD phenotypes.

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders.

Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by the progressive loss of motor neurons and consequent muscle atrophy. Although SMN-targeted therapies have significantly improved survival and motor outcomes, residual muscle weakness remains a major clinical challenge, particularly in patients treated later in the disease course. Myostatin, a potent negative regulator of skeletal muscle mass, has emerged as a promising therapeutic target to address this gap. This review summarizes the preclinical and clinical evidence supporting the modulation of the myostatin pathway in SMA. Preclinical studies have demonstrated that inhibiting myostatin, especially when combined with SMN-enhancing agents, can increase muscle mass, improve motor function, and enhance neuromuscular connectivity in SMA mouse models. These findings provide a strong rationale for translating myostatin inhibition into clinical practice as an adjunctive strategy. Early clinical trials investigating myostatin inhibitors have shown favorable safety profiles and preliminary signs of target engagement. However, large-scale trials have yet to demonstrate widespread, robust efficacy across diverse patient populations. Despite this, myostatin pathway inhibition remains a compelling approach, particularly when integrated into broader treatment paradigms aimed at enhancing motor unit stability and function in individuals with SMA. Further clinical research is essential to validate efficacy, determine optimal timing, and define the patient subgroups most likely to benefit from myostatin-targeted therapies.

Background: Violent TV series and streaming content are increasingly accessible to children, raising concerns about behavioral imitation and psychological effects. This study examined copycat behaviors and associated emotional and somatic symptoms among children who reported watching the age-restricted series Squid Game. Methods: In this observational study of 228 Italian primary school children (aged 8–11), 128 who had watched Squid Game formed the analytic sample. They were categorized into a Copycat Behavior (CB) group or a Non-Copycat Behavior (NCB) group based on self-reported imitation of scenes or games from the series. Parents completed the Child Behavior Checklist (CBCL). Group differences were assessed using Mann–Whitney U tests, and gender distribution was compared with Chi-square tests (α = 0.05). Results: Among viewers, 42 children (32%) engaged in imitation behaviors, typically reenacting game-based violent scenes with friends (52%), siblings (28%), or classmates (20%). Age and gender distributions did not differ between groups. The CB group scored slightly higher on the CBCL Somatic Complaints scale compared with the NCB group (M = 54.12 vs. 52.92; U = 1414.5, p = 0.033), although this difference was small. No significant differences emerged on other CBCL syndrome or broadband scales. Conclusions: Among children engaging in copycat behaviors exhibited a small, subclinical increase in somatic complaints. While causality cannot be inferred, the findings highlight the need to protect vulnerable children—particularly those prone to somatic distress—from unsupervised access to violent, age-inappropriate content. Media literacy for parents and educators, and longitudinal studies including non-viewers are recommended.

Background: Primary nocturnal enuresis (PNE) has been hypothesized to be associated with cognitive impairments, particularly in intelligence and working memory. However, the extent and significance of this relationship remain unclear. This meta-analysis aims to systematically examine the association between PNE and cognitive functioning. Methods: A systematic review and meta-analysis were conducted, including 10 studies with a total of 9987 participants (primary nocturnal enuresis = 1758; control = 8229). Cognitive performance, particularly intelligence quotient scores, was analyzed using pooled statistical methods to determine potential differences between groups. Results: Children with PNE exhibited a mean intelligence quotient score 2.44 points lower than control participants. However, this difference did not reach statistical significance (p = 0.261), and the overall effect size was minimal (t = −1.165). The pooled standard deviation was 13.91, indicating substantial variability across studies. Conclusions: While children with PNE tend to have slightly lower intelligence quotient scores than their peers, the results do not suggest a statistically significant impact on global intelligence. However, the consistent trend observed across studies highlights the need for further research to investigate specific cognitive domains that may be affected by enuresis. Future studies should focus on neurodevelopmental mechanisms and explore potential intervention strategies to address any cognitive vulnerabilities associated with this condition.