Prospects for diagnostics and treatment of neurofibromatosis type 1 in Russia

Abstract

Purpose of the study. Analysis of available data on modern methods of diagnosis and treatment of neurofibromatosis type 1 (NF1) and their application in the Russian Federation. Material and Methods. The search for relevant sources was carried out in the Scopus, Web of Science, PubMed, Elibrary systems, including publications from February 1992 to December 2022. Of the 1873 scientific articles found, 48 were used to write a systematic review. Results. Neurofibromatosis type 1 (NF1) is caused by germline heterozygous mutations in the NF1 gene, which encodes the neurofibromin protein, which suppresses mitogen-activated signaling pathways necessary for cell proliferation. Clinical manifestations of NF1 are similar to Peutz–Jeghers, Laugier–Hunziker, Rusalkab–Muret–Smith, Bannayan–Zonnana, LEOPARD syndromes, neurofibromatosis type 2 and lipomatosis; therefore, to confirm the diagnosis, the most important criterion is the detection of a gene mutation by sequencing, since there are no mutagenesis hotspots in the NF1 gene. To detect 17q11.2 locus microdeletions, MLPA method is used. In Russia, such methods of molecular genetic identification of NF1 were carried out in Moscow and in the Republic of Bashkortostan. Surgical interventions using a neodymium laser and therapy with mitogen-activated protein kinase inhibitors are the most effective for the treatment of tumor syndrome. Scientific results of the use of a surgical laser in the treatment of plexiform neurofibromas and extramedullary tumors of the spinal cord have been published in Russia. Treatment of NF1 with selumetinib in Russia was announced by the interregional public organization for assistance to patients with neurofibromatosis “22/17”, which provides the drug to children with inoperable neurofibromas free of charge. Conclusion. In modern medicine, it is necessary to widely use methods for identifying mutations in the NF1 gene by creating universal panels of targeted sequencing. This will allow not only the differential diagnosis of NF1, but also the identification of the cause of chemoresistance of sporadic malignant neoplasms for the introduction of mitogen-activated protein kinase inhibitors in their treatment. Combination of this method with surgical excision of neurofibromas using a neodymium laser is optimal.

Neurofibromatoses: pathomorphological and clinical polymorphism, efficacy of targeted therapy

“…Нейрофиброматоз 1-го типа -моногенная болезнь с аутосомно-доминантным типом наследования, встречающаяся во всех странах мира со средней частотой в мире 1:3000 населения. Поскольку основным клиническим проявлением НФ1 являются множественные неоплазмы, данное заболевание относится к группе наследственных опухолевых синдромов [6,7].…”