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.

Pediatric pseudotumor cerebri syndrome (PTCS) differs from adult disease in epidemiology, risk factors and clinical presentation. Female predominance and obesity are typically reported after puberty, while secondary forms are more frequent in younger children. Due to limited data on prepubertal patients, this study aimed to analyze clinical features, management and outcomes of pediatric PTCS, focusing on metabolic factors and disease course. We retrospectively analyzed 14 children and adolescents diagnosed with PTCS in a pediatric center between 2015 and 2025, according to Friedman criteria. Data included demographics, pubertal status, body mass index, presenting symptoms, secondary causes, treatments and outcomes over 12 months. Additional post-study follow-up was performed when available. Female predominance was observed regardless of pubertal status. All patients were overweight or obese at diagnosis. Headache was the most frequent presenting symptom (85.7%), often accompanied by visual symptoms. Papilledema was present in all patients. Secondary PTCS occurred in three patients. Treatment included weight loss and acetazolamide in all patients. At 12 months, complete clinical and ophthalmologic remission was achieved in 64.3%. Recurrences occurred in three patients, both early and late: two required surgical interventions. PTCS should be suspected in overweight or obese children and adolescents presenting with persistent headache or visual symptoms, regardless of pubertal status. Early diagnosis, weight control and regular ophthalmologic monitoring are essential to reduce the risk of permanent visual impairment. Long-term follow-up is necessary, as relapses may occur beyond the first year after diagnosis. Prospective studies are warranted to confirm these findings.

TANGO2-deficiency disorder (TDD) is a rare autosomal recessive condition characterised by neurodevelopmental delay, TANGO2 spells, life-threatening metabolic crises, and cardiac arrhythmias. Genotype–phenotype correlations remain poorly defined and the neurobehavioural profile of affected individuals is largely unexplored. We conducted a retrospective multicentre study of five Italian patients with genetically confirmed TDD, identified between June 2023 and May 2025. Clinical, neurophysiological, neuroimaging, genetic, and neurodevelopmental data were collected. Adaptive functioning, cognitive ability, and behavioural profiles were assessed using standardised instruments. All five patients carried biallelic TANGO2 mutations, including two previously unreported variants. Clinical severity ranged from an asymptomatic individual under preventive therapy to a fatal early-onset metabolic crisis. Marked intrafamilial variability was observed in two siblings sharing the same genotype. Systematic neurodevelopmental assessment revealed a spectrum of cognitive and adaptive outcomes, with attentional difficulties identified as a recurrent feature. No metabolic crises or TANGO2 spells were documented following initiation of B-vitamin and cofactor supplementation in surviving patients. This cohort expands the mutational and phenotypic spectrum of TDD and highlights the diagnostic value of TANGO2 testing in patients with neurodevelopmental delay or paroxysmal neurological episodes, even in the absence of metabolic crises. Early supplementation therapy may contribute to clinical stability, though prospective controlled studies are needed.