Abstract
<jats:p>Background. Neurofibromatosis type 1 is a common autosomal-dominant neurocutaneous disorder with broad molecular and clinical heterogeneity. Pediatric patients frequently present early with pigmentary findings, neurodevelopmental issues, and risk of tumor development, including plexiform neurofibromas. In this paper, we aimed to synthesize recent advances in the molecular genetics of neurofibromatosis type 1 and genotype-phenotype correlations, and to illustrate clinical variability through three anonymized pediatric cases. Materials and methods. Narrative review of the literature (2018–2025) focusing on molecular mechanisms, genotype-phenotype correlations, pediatric clinical spectrum, diagnostic strategy, and modern therapies; illustrative case descriptions. Results. Neurofibromatosis type 1 results from pathogenic variants in the NF1 gene, which encodes neurofibromin, a regulator of RAS signaling. Recent large cohorts and domain-specific analyses have refined genotype-phenotype associations (e.g., specific missense variants and exon clusters associated with distinctive manifestations). Targeted therapies (MEK inhibitors) transformed management of inoperable plexiform neurofibromas; regulatory approvals expanded indications and formulations for pediatric use in 2020–2025. Surveillance recommendations emphasize early developmental screening, ophthalmologic and neuroimaging assessments, and multidisciplinary care. Across three pediatric cases, neurofibromatosis type 1 showed marked age-dependent variability, from isolated pigmentary signs to optic pathway glioma and a de novo multisystem phenotype. Molecular confirmation and structured surveillance supported earlier diagnosis, timely detection of complications, and improved family counseling, although prognosis remained poorly predictable from variant class alone. Conclusions. Advances in molecular characterization and targeted treatment options require integration into pediatric care pathways; standardized genotyping and longitudinal follow-up improve prognosis and enable personalized management.</jats:p>