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: 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.