THE ROLE OF MULTIDISCIPLINARY APPROACH IN THE PROCESS OF DIAGNOSING NEUROFIBROMATOSIS, TYPE 1, IN COMBINATION WITH CONGENITAL HEART PATHOLOGY

  2. 2025
  3. THE ROLE OF MULTIDISCIPLINARY APPROACH IN THE PROCESS OF DIAGNOSING NEUROFIBROMATOSIS, TYPE 1, IN COMBINATION WITH CONGENITAL HEART PATHOLOGY

Kuzevanova M. V., Koniushevska A. A., Smyrnova G. S., Gerasymenko V. V., Globa M. V.

THE ROLE OF MULTIDISCIPLINARY APPROACH IN THE PROCESS OF DIAGNOSING NEUROFIBROMATOSIS, TYPE 1, IN COMBINATION WITH CONGENITAL HEART PATHOLOGY

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About the author:

Kuzevanova M. V., Koniushevska A. A., Smyrnova G. S., Gerasymenko V. V., Globa M. V.

Heading:

LITERATURE REVIEWS

Type of article:

Scientific article

Annotation:

Neurofibromatosis type 1 is a complex hereditary disease that poses a challenge to clinicians of any speciality. Affecting numerous organ systems, this disease has a high tendency to develop tumours, primarily damages the peripheral and central nervous system, and requires certain knowledge and constant diagnostic monitoring. Complications of neurofibromatosis type 1 can vary significantly between people, even within the same family. The neurofibromatosis gene NF1 has one of the highest mutation rates, with more than 3700 pathogenic mutation variants described in the literature, requiring careful differential diagnosis. Clinical manifestations of the disease can be highly variable, ranging from exclusively skin lesions to the involvement of various organs, making the development of the disease unpredictable and its prognosis unclear and uncertain. In recent years, the understanding of this disease has improved significantly as a result of the creation of special diagnostic and observation centres. However, the problem of a one-sided view of a patient with neurofibromatosis still remains. It is difficult for an ophthalmologist, neurologist, dermatologist, cardiologist, oncologist and other specialists to analyse the diverse clinical picture of such patients from birth throughout their lives alone, so the role of an interdisciplinary approach with an expert neurofibromatosis coordinator is extremely important for timely referral of patients for additional diagnostic testing and timely treatment and prevention of complications, which is the key to improving the overall quality of life.

Tags:

clinic, diagnostics, heart pathology, interdisciplinary group, neurofibromatosis

Bibliography:

  1. Lalvani S, Brown RM. Neurofibromatosis Type 1: Optimizing Management with a Multidisciplinary Approach. J Multidiscip Healthc. 2024;17:1803-17. DOI: 10.2147/JMDH.S362791.
  2. Karaconji T, Whist E, Jamieson RV, Flaherty MP, Grigg JRB. Neurofibromatosis Type 1: Review and Update on Emerging Therapies. Asia Pac J Ophthalmol. (Phila). 2019;8(1):62-72. DOI: 10.22608/APO. 2018182.
  3. Tamura R. Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis. Int J Mol Sci. 2021;22(11):5850. DOI: 10.3390/ ijms 22115850.
  4. Leśniewski M, Welian-Polus I, Oleksak I, Maliszewska K. Diagnostic and therapeutic process of neurofibromatosis type 1 and type 2. J Educ Health Sport. 2024;63:168-81. DOI: 10.12775/JEHS.2024.63.013.
  5. Pinna V, Daniele P, Calcagni G, Mariniello L, Criscione R, Giardina C, et al. Prevalence, Type, and Molecular Spectrum of NF1 Mutations in Patients with Neurofibromatosis Type 1 and Congenital Heart Disease. Genes (Basel). 2019;10(9):675. DOI: 10.3390/genes10090675.
  6. Peltonen S, Kallionpää RA, Peltonen J. Neurofibromatosis type 1 (NF1) gene: Beyond café au lait spots and dermal neurofibromas. Exp Dermatol. 2017;26(7):645-8. DOI: 10.1111/exd.13212.
  7. Palma MC, Lezana RJM, López MJ, Garrido LDA, Sánchez Linares C, Carmona Tamajón S, et al. Neurofibromatosis type I: mutation spectrum of NF1 in spanish patients. Ann Hum Genet. 2018;82(6):425-36. DOI: 10.1111/ahg.12272.
  8. Friedman JM. Neurofibromatosis 1 Gene Reviews. Seattle (WA): University of Washington; 1998. Available from: https://www.ncbi.nlm. nih.gov/ books/NBK1109/.
  9. Assunto A, Ferrara U, De Luca A, Pivonello C, Lombardo L, Piscitelli A, et al. Isoform-specific NF1 mRNA levels correlate with disease severity in Neurofibromatosis type 1. Orphanet J Rare Dis. 2019;14(1):261. DOI: 10.1186/s13023-019-1223-1.
  10. Ghalavand MA, Asghari A, Farhadi M, Taghizadeh-Hesary F, Garshasbi M, Falah M. The genetic landscape and possible therapeutics of neurofibromatosis type 2. Cancer Cell Int. 2023;23(1):99. DOI: 10.1186/s12935-023-02940-8.
  11. Hiruta R, Saito K, Bakhit M, Fujii M. Current progress in genomics and targeted therapies for neurofibromatosis type 2. Fukushima. J Med Sci. 2023;69(2):95-103. DOI: 10.5387/fms.2023-05.
  12. Farschtschi S, Mautner VF, McLean ACL, Schulz A, Friedrich RE, Rosahl SK. The Neurofibromatoses. Dtsch Arztebl Int. 2020;117(20):354- 60. DOI: 10.3238/arztebl.2020.0354.
  13. Kokkinou E, Roka K, Alexopoulos A, Tsina E, Nikas I, Krallis P, et al. Development of a multidisciplinary clinic of neurofibromatosis type 1 and other neurocutaneous disorders in Greece. A 3-year experience. Postgrad Med. 2019;131(7):445-52. DOI: 10.1080/00325481.2019.1659708.
  14. Bergoug M, Doudeau M, Godin F, Mosrin C, Vallée B, Bénédetti H. Neurofibromin Structure, Functions and Regulation. Cells. 2020;9(11):2365. DOI: 10.3390/cells9112365.
  15. Bergqvist C, Servy A, Valeyrie-Allanore L, Ferkal S, Combemale P, Wolkenstein P. Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966. Orphanet J Rare Dis. 2020;15(1):37. DOI: 10.1186/s13023-020-1310-3.
  16. Wang W, Wei CJ, Cui XW, Li YH, Gu YH, Gu B, et al. Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1. Front Neurol. 2021;12:704639. DOI: 10.3389/fneur.2021.704639.
  17. Legius E, Messiaen L, Wolkenstein P, Pancza P, Avery RA, 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. DOI: 10.1038/s41436-021-01170-5.
  18. Kallionpää RA, 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. DOI: 10.1038/gim.2017.215.
  19. Kehrer-Sawatzki H, Cooper DN. 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. DOI: 10.1007/ s00439-021-02410-z.
  20. Miller DT, Freedenberg D, Schorry E, Ullrich NJ, Viskochil D, Korf BR. Health Supervision for Children With Neurofibromatosis Type 1. Pediatrics. 2019;143(5):e20190660. DOI: 10.1542/peds.2019-0660.
  21. Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers. 2017;3:17004. DOI: 10.1038/nrdp.2017.4.
  22. Chen H, Li X, Liu X, Wang J, Zhang Z, Wu J, et al. Clinical and mutation profile of pediatric patients with RASopathy-associated hypertrophic cardiomyopathy: results from a Chinese cohort. Orphanet J Rare Dis. 2019;14(1):29. DOI: 10.1186/s13023-019-1010-z.
  23. Calcagni G, Limongelli G, D’Ambrosio A, Gesualdo F, Digilio MC, Baban A et al. Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results. Int J Cardiol. 2017:245:92-98. DOI: 10.1016/j.ijcard.2017.07.068.
  24. Ortonne N, Wolkenstein P, Blakeley JO, Korf B, Plotkin SR, Riccardi VM. Cutaneous neurofibromas: Current clinical and pathologic issues. Neurology. 2018;91(2.1):5-13. DOI: 10.1212/WNL.0000000000005792.
  25. Fenot M, Stalder JF, Barbarot S. Juvenile xanthogranulomas are highly prevalent but transient in young children with neurofibromatosis type 1. J Am Acad Dermatol. 2014;71(2):389-90. DOI: 10.1016/j.jaad.2014.02.049.
  26. Paulus S, Koronowska S, Fölster-Holst R. Association Between Juvenile Myelomonocytic Leukemia, Juvenile Xanthogranulomas and Neurofibromatosis Type 1: Case Report and Review of the Literature. Pediatr Dermatol. 2017;34(2):114-8. DOI: 10.1111/pde.13064.
  27. Dombi E, Baldwin A, Marcus LJ, Fisher MJ, 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. DOI: 10.1056/NEJMoa1605943.
  28. Yoo HK, Porteous A, Ng A, Haria K, Griffiths A, Lloyd A, et al. Impact of neurofibromatosis type 1 with plexiform neurofibromas on the health-related quality of life and work productivity of adult patients and caregivers in the UK: a cross-sectional survey. BMC Neurol. 2023;23(1):419. DOI: 10.1186/s12883-023-03429-7.
  29. Staser K, Yang FC, Clapp DW. Pathogenesis of plexiform neurofibroma: tumor-stromal/hematopoietic interactions in tumor progression. Annu Rev Pathol. 2012;7:469-95. DOI: 10.1146/annurev-pathol-011811-132441.
  30. Vasconcelos RAT, Coscarelli PG, Alvarenga RP, Acioly MA. Malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1. Arq Neuropsiquiatr. 2017;75(6):366-71. DOI: 10.1590/0004-282X2017 0052.
  31. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834-43. DOI: 10.1016/ S1474-4422(14)70063-8.
  32. Cimino PJ, Gutmann DH. Neurofibromatosis type 1. Handb Clin Neurol. 2018;148:799-811. DOI: 10.1016/B978-0-444-64076-5.00051-X.
  33. Miraglia E, Moliterni E, Iacovino C, Roberti V, Laghi A, Moramarco A, et al. Cutaneous manifestations in neurofibromatosis type 1. Clin Ter. 2020;171(5):e371-e377. DOI: 10.7417/CT.2020.2242.
  34. Shofty B, Barzilai O, Khashan M, Lidar Z, Constantini S. Spinal manifestations of Neurofibromatosis type 1. Childs Nerv Syst. 2020;36(10):2401-8. DOI: 10.1007/s00381-020-04754-9.
  35. Helfferich J, Nijmeijer R, Brouwer OF, Boon M, Fock A, Hoving EW, et al. Neurofibromatosis type 1 associated low grade gliomas: A comparison with sporadic low grade gliomas. Crit Rev Oncol Hematol. 2016;104:30-41. DOI: 10.1016/j.critrevonc.2016.05.008.
  36. Mahdi J, Shah AC, Sato A, Morris SM, McKinstry RC, Listernick R, et al. A multi-institutional study of brainstem gliomas in children with neurofibromatosis type 1. Neurology. 2017;88(16):1584-9. DOI: 10.1212/WNL.0000000000003881.
  37. Prada CE, Hufnagel RB, Hummel TR, Lovell AM, Hopkin RJ, Saal HM, et al. The Use of Magnetic Resonance Imaging Screening for Optic Pathway Gliomas in Children with Neurofibromatosis Type 1. J Pediatr. 2015;167(4):851-6. DOI: 10.1016/j.jpeds.2015.07.001.
  38. Bianchi F, Cocilovo FM, Ruggiero A, Tamburrini G. Optic Pathway Gliomas: The Trends of Basic Research to Reduce the Impact of the Disease on Visual Function. Advances and Technical Standards in Neurosurgery. 2023;48:123-37. DOI: 10.1007/978-3-031-36785-4_6.
  39. Anastasaki C, Orozco P, Gutmann DH. RAS and beyond: the many faces of the neurofibromatosis type 1 protein. Dis Model Mech. 2022;15(2):dmm049362. DOI: 10.1242/dmm.049362.
  40. Ejerskov C, Raundahl M, Gregersen PA, Handrup MM. Clinical features and disease severity in patients with mosaic neurofibromatosis type 1: a single-center study and literature review. Orphanet J Rare Dis. 2021;16(1):180. DOI: 10.1186/s13023-021-01796-3.
  41. Kinori M, Hodgson N, Zeid JL. Ophthalmic manifestations in neurofibromatosis type 1. Surv Ophthalmol. 2018;63(4):518-33. DOI: 10.1016/j.survophthal.2017.10.007.
  42. Tsang DS, Murphy ES, Merchant TE. Radiation Therapy for Optic Pathway and Hypothalamic Low-Grade Gliomas in Children. Int J Radiat Oncol Biol Phys. 2017;99(3):642-51. DOI: 10.1016/j.ijrobp.2017.07.023.
  43. Wang D, Ge L, Guo Z, Li Y, Zhu B, Wang W, et al. Efficacy and Safety of Trametinib in Neurofibromatosis Type 1-Associated Plexiform Neurofibroma and Low-Grade Glioma: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel). 2022;15(8):956. DOI: 10.3390/ ph 15080956.
  44. Fangusaro J, Onar-Thomas A, Poussaint TY, Wu S, Ligon AH, Lindeman N, et al. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019;20(7):1011-22. DOI: 10.1016/S1470-2045(19)30277-3.
  45. Patil S, Chamberlain RS. Neoplasms associated with germline and somatic NF1 gene mutations. Oncologist. 2012;17(1):101-16. DOI: 10.1634/ theoncologist.2010-0181.
  46. Seminog OO, Goldacre MJ. Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: population-based record-linkage study. Br J Cancer. 2013;108(1):193-8. DOI: 10.1038/ bjc.2012.535.
  47. Uusitalo E, Kallionpää RA, Kurki S, Rantanen M, Pitkäniemi J, Kronqvist P, et al. Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors. Br J Cancer. 2017;116(2):211-7. DOI: 10.1038/bjc.2016.403.
  48. Madanikia SA, Bergner A, Xiaobu Y, O’Neill Blakeley J. Increased risk of breast cancer in women with NF1. Am J Med Genet. 2012;158A(12):3056-60. DOI: 10.1002/ajmg.a.35550.
  49. Képénékian L, Mognetti T, Lifante JC, Giraudet AL, Houzard C, Pinson S, et al. Combemale Patrick. Interest of systematic screening of pheochromocytoma in patients with neurofibromatosis type 1. Eur J Endocrinol. 2016;175(4):335-44. DOI: 10.1530/eje-16-0233.
  50. Gruber LM, Erickson D, Babovic-Vuksanovic D, Thompson GB, Young WF Jr, Bancos I. Pheochromocytoma and paraganglioma in patients with neurofibromatosis type 1. J Clin Endocrinol. 2016;86(1):141-9. DOI: 10.1111/cen.13163.
  51. Salvi PF, Lorenzon L, Caterino S, Antolino L, Antonelli MS, Balducci G. Gastrointestinal stromal tumors associated with neurofibromatosis 1: a single centre experience and systematic review of the literature including 252 cases. Int. J Surg Oncol. 2013;2013:398570. DOI: 10.1155/2013/ 398570.
  52. Landry JP, Schertz KL, Chiang YJ, Bhalla AD, Yi M, Keung EZ, et al. Comparison of Cancer Prevalence in Patients With Neurofibromatosis Type 1 at an Academic Cancer Center vs in the General Population From 1985 to 2020. JAMA Netw Оpen. 2021;4(3):e210945. DOI: 10.1001/jamanetwork open.2021.0945.
  53. İncecik F, Hergüner ÖM, Alınç Erdem S, Altunbaşak Ş. Neurofibromatosis type 1 and cardiac manifestations. Turk Kardiyol Dern Ars. 2015;43(8):714-6. DOI: 10.5543/tkda.2015.27557.
  54. Cutruzzolà A, Irace C, Frazzetto M, Sabatino J, Gullace R, De Rosa S, et al. Functional and morphological cardiovascular alterations associated with neurofibromatosis 1. Sci Rep. 2020;10(1):12070. DOI: 10.1038/s41598-020-68908-0.
  55. Spinnato P, Facchini G, Tetta C, Lotrecchiano L, Colangeli M, Bazzocchi A, et al. Neurofibromatosis type-1-associated diffuse lung disease in children. Pediatr Pulmonol. 2019;54(11):1760-4. DOI: 10.1002/ppul.24481.
  56. Kaspiris A , Savvidou D, Vasiliadis ES, Hadjimichael AC, Melissaridou D, Iliopoulou-Kosmadaki S, et al. Current Aspects on the Pathophysiology of Bone Metabolic Defects during Progression of Scoliosis in Neurofibromatosis Type 1. J Clin Med. 2022;11(2):444. DOI: 10.3390/jcm 11020444.
  57. Shofty B, Barzilai O, Khashan M, Lidar Z, Constantini S. Spinal manifestations of Neurofibromatosis type 1. Childs Nerv Syst. 2020;36(10):2401-8. DOI: 10.1007/s00381-020-04754-9.
  58. Bizzarri C, Bottaro G. Endocrine implications of neurofibromatosis 1 in childhood. Horm. Res. Paediatr. 2015;83(4):232-41. DOI: 10.1159/ 000369802.
  59. Well L, Jaeger A, Kehrer-Sawatzki H, Farschtschi S, Avanesov M, Sauer M, et al. The effect of pregnancy on growth-dynamics of neurofibromas in Neurofibromatosis type 1. PLoS One. 2020;15(4):e0232031. DOI: 10.1371/journal.pone.0232031.
  60. Kehrer-Sawatzki H, Cooper DN. 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. Human Genetics. 2021;141(2):177-91. DOI: 10.1007/s00439-021-02410-z.
  61. Tadini G, Milani D, Menni F, Pezzani L, Sabatini C, Esposito S. Is it time to change the neurofibromatosis 1 diagnostic criteria? Eur J Intern Med. 2014;25(6):506-10. DOI: 10.1016/j.ejim.2014.04.004.
  62. Renzi S, Michaeli O, Salvador H, Alderete D, Ponce NF, Zapotocky M, et al. Bevacizumab for NF2-associated vestibular schwannomas of childhood and adolescence. Pediatr Blood Cancer. 2020;67(5):e28228. DOI: 10.1002/ pbc.28228.
  63. Jiramongkolchai P, Schwartz MS, Friedman RA. Management of Neurofibromatosis Type 2-Associated Vestibular Schwannomas. Otolaryngol Clin North Am. 2023;56(3):533-41. DOI: 10.1016/j.otc.2023. 02.012.
  64. Gross AM, Wolters PL, Dombi E, Baldwin A, Whitcomb P, Fisher MJ, et al. Selumetinib in Children with Inoperable Plexiform Neurofibromas. N Engl J Med. 2020;382(15):1430-42. DOI: 10.1056/NEJMoa1912735.
  65. Gross AM, Glassberg B, Wolters PL, Dombi E, Baldwin A, Whitcomb P, et al. Selumetinib in children with neurofibromatosis type 1 and asymptomatic inoperable plexiform neurofibroma at risk for developing tumor-related morbidity. Neuro Oncol. 2022;24(11):1978-88. DOI: 10.1093/neuonc/ noac109.
  66. Anforth R, Liu M, Nguyen B, Uribe P, Kefford R, Clements A, et al. Acneiform eruptions: a common cutaneous toxicity of the MEK inhibitor trametinib. Australas J Dermatol. 2014;55(4):250-4. DOI: 10.1111/ajd. 12124.
  67. Klesse LJ, Jordan JT, Radtke HB, Rosser T, Schorry E, Ullrich N, et al. The Use of MEK Inhibitors in Neurofibromatosis Type 1-Associated Tumors and Management of Toxicities. Oncologist. 2020;25(7):e1109-e1116. DOI: 10.1634/theoncologist.2020-0069.
  68. de Blank PMK, Gross AM, Akshintala S, Blakeley JO, Bollag G, Cannon A, et al. MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus. Neuro Oncol. 2022;24(11):1845-56. DOI: 10.1093/neuonc/noac165.
  69. Miller J, Perotti V, Moore P. Massive spontaneous haemorrhage in a plexiform neurofibroma: A case report and discussion of the literature. J Clin Neurosci. 2020;80:229-31. DOI: 10.1016/j.jocn.2020.08.024.
  70. Winter N, Dohrn MF, Wittlinger J, Loizides A, Gruber H, Grimm A. Role of high-resolution ultrasound in detection and monitoring of peripheral nerve tumor burden in neurofibromatosis in children. Childs Nerv Syst. 2020;36(10):2427-32. DOI: 10.1007/s00381-020-04718-z.
  71. Donado C, Nedeljkovic K, Wangnamthip S, Solodiuk JC, Bourgeois FT, Berde CB. Trends in Gabapentin and Pregabalin Prescribing in a Tertiary Pediatric Medical Center. Hosp. Pediatr. American Academy of Pediatrics. 2021;11(8):909-14. DOI: 10.1542/hpeds.2020-003582.
  72. Walker SM. Neuropathic pain in children: Steps towards improved recognition and management. EBioMedicine. 2020;62:103124. DOI: 10.1016/j.ebiom.2020.103124.
  73. Poplausky D, Young JN, Tai H, Rivera-Oyola R, Gulati N, Brown RM. Dermatologic manifestations of neurofibromatosis type 1 and emerging treatments. Cancers. 2023;15(10):2770. DOI: 10.3390/cancers15102770.
  74. Stewart DR, Korf BR, Nathanson KL, Stevenson DA, Yohay K. Care of adults with neurofibromatosis type 1: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018;20(7):671-82. DOI: 10.1038/gim.2018.28.

Publication of the article:

«Bulletin of problems biology and medicine», 2025 Issue 1, 176, 43-61 pages, index UDC 616.833-006.48-06:616.12]-07:575.1

DOI:

10.29254/2077-4214-2025-1-176-43-61

2025 Issue 1, 176
clinic diagnostics heart pathology interdisciplinary group neurofibromatosis
26.03.2025
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