Epidemiology of neurofibromatosis in children in the Russian Federation over 2015–2024

Neurofibromatosis is an orphan disease of the phakomatose group, the timely treatment of which helps to reduce the burden of pain and surgical interventions. Aim. To analyze the trend in the neurofibromatosis epidemic in children over the past decade in the context of timely diagnosis of the disease and early treatment initiation.

Materials and methods. The authors have analyzed official statistical data (federal statistical observation form No.12) for 2015–2024 for Russia as a whole and by urban and rural population, as well as by constituent entity of the Russian Federation.

Results. The prevalence of neurofibromatosis in 0–4 year children increased from 3.9 in 2016 to 7.1 per 100,000 children of the corresponding age in 2024; in children aged 5–9 years — from 5.3 to 9.4; and in children aged 10–14 years — from 11.7 to 18.2; The incidence in 0–14 years children aged increased from 7.8 in 2015 to 16.6 in 2024, and in children aged 15–17 years — from 5.8 to 12.1. There was an increase in the incidence rate in 0–14 year children – from 1.3 in 2015 to 1.8 in 2023. The incidence rate in adolescents changed statistically insignificantly, amounting to 0.8 per 100,000 children aged of 15–17 years in both 2015 and 2024. Only 3.5% of children are detected during preventive examinations. The incidence of neurofibromatosis in rural residents is significantly lower than in urban areas. The average 10-year prevalence rate of neurofibromatosis in children aged 0–17 years varies across regions from 0.3 to 27.2 per 100,000 population (the interquartile range equaled to 7.2); the incidence rate ranges from 0.0 to 5.1. The highest values ​​are associated with regions with an ethnic and genetic prevalence of the Finno-Ugric population.

Conclusion. The increase in the incidence of neurofibromatosis is associated with underdiagnosis of this disease and low detection rates during preventive examinations. Given the availability of treatments that can reduce the burden of pain syndrome and surgical interventions, it is advisable to realize measures to identify patients with neurofibromatosis in organized children’s groups, for example, periodic surveys of schoolchildren for the neurofibromatosis symptoms, using online tools.

Contribution:
Vitkovskaya I.P. — concept and design of the study, writing the text;
Sterlikov S.A. — statistical analysis, writing the text;
Zelenova O.V. — management of scientific collaboration and coordination;
Oskov Yu.I. — collection of statistical material and methodological consulting;
Pankova Ya.Yu. — support for research planning, editing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: September 15, 2025
Accepted: October 02, 2025
Published: October 30, 2025

1. Farschtschi S.C., Mainka T., Glatzel M., Hannekum A-L., Hauck M., Gelderblom M., et al. C-fiber loss as a possible cause of neuropathic pain in Schwannomatosis. Int. J. Mol. Sci. 2020; 21(10): 3569. https://doi.org/10.3390/ijms21103569

2. Kresak J.L., Walsh M. Neurofi bromatosis: A review of NF1, NF2, and Schwannomatosis. J. Pediatr. Genet. 2016; 5(2): 98–104. https://doi.org/10.1055/s-0036–1579766

3. Lee T.J., Chopra M., Kim R.H., Parkin P.C., Barnett-Tapia C. Incidence and prevalence of neurofibromatosis type 1 and 2: a systematic review and meta-analysis. Orphanet J. Rare Dis. 2023; 18(1): 292. https://doi.org/10.1186/s13023-023-02911-2

4. Le C., Thomas A., Lui F. Neurofibromatosis. Treasure Island (FL): StatPearls Publishing; 2025. Available at: https://ncbi.nlm.nih.gov/books/NBK459329/

5. Makashova E.S., Karandasheva K.O., Zolotova S.V., Ginzberg M.A., Dorofeeva M.Yu., Galkin M.V., et al. Neurofibromatosis: analysis of clinical cases and new diagnostic criteria. Nervno-myshechnye bolezni. 2022; 12(1): 39–48. https://doi.org/10.17650/2222-8721-2022-12-1-39-48 https://elibrary.ru/utftke (in Russian)

6. Tsotsonava Zh.M., Tkacheva N.V., Gasanova S.R., Dzeitova A.M. Neurofibromatoses: pathomorphological and clinical polymorphism, effectiveness of targeted therapy. Arkhiv pediatrii i detskoy khirurgii. 2024; 2(1): 196–207. https://doi.org/10.31146/2949-4664-apps-2-1-196-207 https://elibrary.ru/tubxwi (in Russian)

7. Gvozdev A.A., Adrianov M.M., Kotlyarov P.M. Extended neurofibromatosis of the central nervous system, casually revealed at a magnitno-resonant tomography (clinical supervision). 2010; (2): 44–8. https://elibrary.ru/nxpwth (in Russian)

8. Mustafin R.N., Bermisheva M.A., Valiev R.R., Khusnutdinova E.K. Neurofibromatosis type 1: results of our own study (Republic of Bashkortostan). Uspekhi molekulyarnoy onkologii. 2021; 8(1): 17–25. https://doi.org/10.17650/2313-805X-2021-8-1-17-25 https://elibrary.ru/ykphbd (in Russian)

9. Resolution of the Expert council on the problems of diagnosis and treatment of patients with plexiform neurofibromas. Rossiyskiy zhurnal detskoy gematologii i onkologii. 2021; 8(2): 144–52. https://doi.org/10.21682/2311-1267-2021-8-2-144-152 https://elibrary.ru/fafyha (in Russian)

10. Makashova E.S., Zolotova S.V., Kostyuchenko V.V., Galkin M.V., Ginzberg M.A., Danilov G.V., et al. Neurofibromatosis 2: new perspectives in treatment (case report). Neurokhirurgiya. 2021; 23(1): 109–18. https://doi.org/10.17650/1683-3295-2021-23-1-109-118 https://elibrary.ru/ojgmzw (in Russian)

11. Karandasheva K.O., Pashchenko M.S., Anoshkin K.I., Kuznetsova E.B., Tanas A.S., Strelnikov V.V. Neurofibromatosis genetic testing: cohort study. Медицинская генетика. 2020; 19(6): 10–1. https://doi.org/10.25557/2073-7998.2020.06.10-11 https://elibrary.ru/aywmsz (in Russian)

12. Zarichansky V.A., Chkadua T.Z., Egiazaryan A.K., Sogachev G.V. Modern concept of generalized neurofibromatosis type I: diagnostics, treatment. Golova i sheya. Rossiyskiy zhurnal. 2023; 11(1): 28–36. https://doi.org/10.25792/HN.2023.11.1.28-36 https://elibrary.ru/mbvnpu (in Russian)

13. Gross A.M., Wolters P.L., Dombi E., Baldwin A., Whitcomb P., Fisher M.J., et al. Selumetinib in children with inoperable plexiform neurofibromas. N. Engl. J. Med 2020; 382(15): 1430–42. https://doi.org/10.1056/NEJMOA1912735

14. Baldo F., Grasso A.G., Cortellazzo Wiel L., Maestro A., Trojniak M.P., Murru F.M., et al. Selumetinib in the treatment of symptomatic intractable plexiform neurofibromas in neurofibromatosis type 1: a prospective case series with emphasis on side effects. Paediatr. Drugs. 2020; 22(4): 417–23. https://doi.org/10.1007/s40272-020-00399-y

15. Santo V.E., Passos J., Nzwalo H., Carvalho I., Santos F., Martins C., et al. Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience. J. Neurooncol. 2020; 147(2): 459–63. https://doi.org/10.1007/s11060-020-03443-6

16. Sakhanova A.Sh., Kenzhebaeva K.A., Babiy D.V., Beysenova A.K., Mukhamed M., Bayazitova Zh.K. Neurofibromatosis in children. 2017; (1): 47–55. https://elibrary.ru/mknkou (in Russian)

17. Nakhusheva F.I. Neurofibromatosis type 1: short review and clinical case. Archives of pediatrics and pediatric surgery. 2024; 2(2): 95–102. https://doi.org/10.31146/2949-4664-apps-2-2-95-102 https://elibrary.ru/nzyjdc (in Russian)

18. Miraglia E., Moliterni E., Iacovino C., Roberti V., Laghi A., Moramarco A., et al. Cutaneous manifestations in neurofi bromatosis type 1. Clin. Ter. 2020; 171(5): e371–7. https://doi.org/10.7417/CT.2020.2242

19. Jett K., Friedman J.M. Clinical and genetic aspects of neurofibromatosis 1. Genet. Med. 2010; 12(1): 1–11. https://doi.org/10.1097/GIM.0b013e3181bf15e3

20. Bergqvist C., Servy A., Valeyrie-Allanore L., Ferkal S., Combemale P., Wolkenstein P., et al. NF France Network. Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966. Orphanet J. Rare Dis. 2020; 15(1): 37. https://doi.org/10.1186/s13023-020-1310-3

21. Ferner R.E., Huson S.M., Thomas N., Moss C., Willshaw H., Evans D.G., et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J. Med. Genet. 2007; 44(2): 81–8. https://doi.org/10.1136/jmg.2006.045906

22. Karaconji T., Whist E., Jamieson R. V., Flaherty M.P., Grigg J.R.B. Neurofibromatosis type 1: review and update on emerging therapies. Asia Pac. J. Ophthalmol. (Phila). 2019; 8(1): 62–72. https://doi.org/10.22608/APO.2018182

23. Kehrer-Sawatzki H., Cooper D.N. Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants. Hum. Genet. 2022; 141(2): 177–91. https://doi.org/10.1007/s00439-021-02410-z

24. Karwacki M.W., Wysocki M., Perek-Polnik M., Jatczak-Gaca A. Coordinated medical care for children with neurofibromatosis type 1 and related RASopathies in Poland. Arch. Med. Sci. 2019; 17(5): 1221–31. https://doi.org/10.5114/aoms.2019.85143

25. Dombi E., Baldwin A., Marcus L.J., Fisher M.J., Weiss B., Kim A., et al. Activity of selumetinib in Neurofibromatosis type 1-related plexiform Neurofibromas. N. Engl. J. Med. 2016; 375(26): 2550–60. https://doi.org/10.1056/NEJMoa1605943

26. Mautner V.F., Asuagbor F. A., Dombi E., Fünsterer C., Kluwe L., Wenzel R., et al. Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1. Neuro Oncol. 2008; 10(4): 593–8. https://doi.org/10.1215/15228517-2008-011

27. Bachir S., Shah S., Shapiro S., Koehler A., Mahammedi A., Samy R.N., et al. Neurofibromatosis type 2 (NF2) and the implications for vestibular schwannoma and meningioma pathogenesis. Int. J. Mol. Sci. 2021; 22(2): 690. https://doi.org/10.3390/ijms22020690

28. Evans D.G., King A. T., Bowers N. L., Tobi S., Wallace A. J., Perry M., et al. Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing. Genet. Med. 2019; 21(7): 1525–33. https://doi.org/10.1038/s41436-018-0384-y

29. Deev I.A., Kobyakova O.S., Starodubov V.I., Aleksandrova G.A., Golubev N.A., Oskov Yu.I., et al. General Morbidity of the Russian Child Population (0-14 Years Old) in 2024. Statistical Materials [Obshchaya zabolevaemost’ detskogo naseleniya Rossii (0-14 let) v 2024 godu. Statisticheskie materialy]. Moscow; 2025. (in Russian)

30. Deev I.A., Kobyakova O.S., Starodubov V.I., Aleksandrova G.A., Golubev N.A., Oskov Yu.I., et al. Morbidity of the Russian Child Population (0-14 Years) in 2024 with a First-Time-in-Life Diagnosis. Statistical Materials [Zabolevaemost’ detskogo naseleniya Rossii (0-14 let) v 2024 godu s diagnozom, ustanovlennym vpervye v zhizni. Statisticheskie materialy]. Moscow; 2025. (in Russian)

31. Iheanacho I., Yoo H.K., Yang X., Dodman S., Hughes R., Amin S. Epidemiological and clinical burden associated with plexiform neurofibromas in pediatric neurofibromatosis type-1 (NF-1): a systematic literature review. Neurol. Sci. 2022; 43(2): 1281–93. https://doi.org/10.1007/s10072-021-05361-5

32. Nazarova A.F. Genetics and phylogenesis of Finno-Ugric populations. Al’manakh Prostranstvo i Vremya. 2013; 4(1): 15. https://elibrary.ru/rsqgqv (in Russian)

33. Loginova N.N., Rebrova T.P. Population dynamics of Finno-Ugric peoples. Finno-ugorskiy mir. 2013; (3): 89–97. https://elibrary.ru/scdcyz (in Russian)

34. Lammert M., Friedman J.M., Kluwe L., Mautner V.F. Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch. Dermatol. 2005; 141(1): 71–4. https://doi.org/10.1001/archderm.141.1.71

35. Orraca M., Morejón G., Cabrera N., Menéndez R., Orraca O. Neurofibromatosis 1 prevalence in children aged 9–11 years, Pinar del Río Province, Cuba. MEDICC Review. 2014; 16(3-4): 22–6. https://doi.org/10.37757/mr2014.v16.n3-4.6

36. Garty B.Z., Laor A., Danon Y.L. Neurofibromatosis type 1 in Israel: survey of young adults. J. Med. Genet. 1994; 31(11): 853–7. https://doi.org/10.1136/jmg.31.11.853

37. Anderson M.K., Johnson M., Thornburg L., Halford Z. A review of selumetinib in the treatment of neurofibromatosis type 1-related plexiform neurofibromas. Ann. Pharmacother. 2022; 56(6): 716–26. https://doi.org/10.1177/10600280211046298

38. Legius E., Messiaen L., Wolkenstein P., Pancza P., Avery R. A., Berman Y., et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet. Med. 2021; 23(8): 1506–13. https://doi.org/10.1038/s41436-021-01170-5

39. Duong T.A., Sbidian E., Valeyrie-Allanore L., Vialette C., Ferkal S., Hadj-Rabia S., et al. Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980–2006 in France. Orphanet J. Rare Dis. 2011; 6: 18. https://doi.org/10.1186/1750-1172-6-18

40. Kallionpää R.A., Uusitalo E., Leppävirta J., Pöyhönen M., Peltonen S., Peltonen J. Prevalence of neurofibromatosis type 1 in the Finnish population. Genet. Med. 2018; 20(9): 1082–6. https://doi.org/10.1038/gim.2017.215