Аннотация
Relevance: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder characterized by marked clinical variability and a risk of developing plexiform neurofibromas, which may lead to significant functional impairment and the potential for malignant transformation. The study of clinical and genetic features of rare and severe forms of plexiform neurofibromas remains an important task for timely diagnosis and selection of optimal treatment strategies.The study aimed to present a clinic-genetic comparison of two unrelated patients with neurofibromatosis type 1 carrying an identical pathogenic NF1 variant (p.Arg2496*), and to evaluate its possible association with the development of extensive limb plexiform neurofibromas and its clinical implications for follow-up strategy and targeted therapy initiation.Materials and Methods: A comprehensive clinical, instrumental, and molecular genetic evaluation was performed in two patients. Diagnostic procedures included clinical and neurological examination, magnetic resonance imaging (MRI) of the limbs and nervous system (1.5 Tesla), and genetic testing of the NF1 gene using next-generation sequencing (NGS) with the Illumina myeloid panel. Data analysis was conducted in accordance with established clinical criteria for NF1.Results: Both patients were found to harbor an identical heterozygous single-nucleotide substitution Chr17:29679366C>T (p.Arg2496*), resulting in a premature stop codon and classified as likely pathogenic. The clinical presentation included large, inoperable plexiform neurofibromas of the lower limb, tibial deformity and elongation, foot thickening, gait disturbance, and pain syndrome. The disease showed a progressive course, with more severe manifestations observed in the adult patient.Conclusion: The presented cases highlight the significant role of molecular genetic diagnostics in confirming NF1 and justifying the early initiation of targeted therapy with MEK inhibitors in patients with inoperable plexiform neurofibromas. The findings emphasize the need for dynamic follow-up and timely initiation of pathogenetic treatment to improve patients’ quality of life.