Nörofibromatozis Tip 1 Tanısı ile İzlenen Hastaların Klinik Özellikleri: Tek Merkez Deneyimi

Yıl 2022, Cilt: 16 Sayı: 6, 507 - 511, 30.11.2022

Canan Üstün , Mutluay Arslan

https://doi.org/10.12956/tchd.984636

Cited By: 1

Öz

Amaç: Nörokutanöz sendromlar sinir sistemini ve cildi tutan bir grup hastalıktır. Bunların arasında en sık görülen nörofibromatozis tip 1’dir (NF1). Bu çalışmanın amacı Gülhane Eğitim ve Araştırma Hastanesi Çocuk Nörolojisi Poliklini’ğinde izlenen NF1 tanılı hastaların klinik özelliklerini değerlendirmektir.

Gereç ve Yöntemler: Kasım 2016-Mart 2021 tarihleri arasında NF1 tanılı toplam 29 hastanın dosya kayıtları geriye dönük olarak gözden geçirildi. Hastaların aile öyküleri, demografik ve klinik özellikleri incelendi.

Bulgular: Hastaların 17’si (%59) erkek, 12’si (%41) kızdı. 10 hastada (%34.4) aile öyküsü mevcuttu. Hastaların 12’sinde (%41.3) NF1 geninde mutasyon saptanmıştı. Hastaların tamamında cafe au lait lekeleri mevcutken, aksiller ve/veya inguinal çillenmeye 18 hastada (%62) rastlandı. 10 hastada (%34.4) kognitif bozukluklar, 3 hastada (%10.3) epilepsi ve 2 hastada (6.9) makrosefali vardı. Lisch nodülü 10 hastada (%34.4) izlenirken, hiçbir hastada optik glioma rastlanmadı. Hastalar maligniteler açısından değerlendirildiğinde 3 hastada (%10.3) periferal nörofibrom, 1 hastada (%3.45) beyin sapı gliomu, 1 hastada (%3.45) akut miyeloid lösemi saptandı.

Sonuç: NF1 çoklu sistem tutulumu yapan geniş yelpazeli bir hastalıktır. Hastalar çok farklı klinik bulgular ile karşımıza çıkabilir. Makrosefali, öğrenme güçlüğü gibi nonspesifik nörolojik yakınmalarla çocuk nörolojisi polikliniğine başvuran hastalar dikkatli bir göz ve deri muayenesi ile NF1 tanısı alabilir. Hastalığın klinik özelliklerinin sıklığının bilinmesi tanı konulmasında yardımcı olacaktır. 

Anahtar Kelimeler

Nörofibromatozis tip 1, çocuk, klinik özellikler, genetik

Clinical Characteristics of Patients with Neurofibromatosis Type 1: A Single Center Experience

Öz

Objective: Neurocutaneous syndromes are a group of diseases involving the nervous system and skin. Among them, the most common is neurofibromatosis type 1 (NF1). The clinical course of NF1 can be heterogeneous and complex. The aim of this study is to evaluate the clinical features of patients with neurofibromatosis type 1 followed in the Gulhane Training and Research Hospital Pediatric Neurology Outpatient Clinic.

Materials and Methods: File records of 29 patients with neurofibromatosis type 1 between November 2016 and March 2021 were retrospectively reviewed. Family histories, demographic and clinical characteristics of the patients were examined.

Results: Seventeen (59%) patients were male and 12 (41%) were female. Patient ages ranged from 2 to 15. There was a family history in 10 patients (34.4%). Genetic examination was planned in 17 of the patients, and mutations in the NF1 gene were detected in 10 (34.4%) of them. Genetic examination of seven patients had not yet been concluded. While all patients had cafe au lait spots, axillary and/or inguinal freckling was observed in 18 patients (62%). 10 patients (34.4%) had learning difficulties and cognitive disorders, 3 patients (10.3%) had epilepsy and 2 patients (6.9%) had macrocephaly. Magnetic Resonance Imaging (MRI) was performed in 16 patients. Hyperintense lesions were detected on T2-weighted images in 9 patients (31%), ventricular enlargement in 1 patient (3.45%), cavernous hemangioma and brain stem glioma in 1 patient (3.45%). While Lisch nodule was observed in 10 patients (34.4%), optic glioma was not found in any patient. When the patients were evaluated in terms of malignancies, peripheral neurofibroma was found in 3 patients (10.3%), brain stem glioma in 1 patient (3.45%), and acute myeloid leukemia in 1 patient (3.45%).

Conclusion: NF1 is a wide spectrum disease with multisystem involvement. Patients may present with very different clinical findings. Patients who presented to the pediatric neurology outpatient clinic with nonspecific neurological complaints such as macrocephaly and learning difficulties can be diagnosed with NF1 with a careful eye and skin examination. Knowing the frequency of the clinical features of the disease will help in making the diagnosis.

Anahtar Kelimeler

Neurofibromatosis type 1, child, clinical features, genetics

Kaynakça

• 1. Schraepen C, Donkersloot P, Duyvendak W, Plazier M, Put E, Roosen G, et al. What to know about schwannomatosis: a literature review. Br J Neurosurg 2020:1-4. doi: 10.1080/02688697.2020.1836323.
• 2. Ghalayani P, Saberi Z, Sardari F. Neurofibromatosis type I (von Recklinghausen’s disease): A family case report and literature review. Dent Res J (Isfahan) 2012;9:483-8.
• 3. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 2010;152A:327-32.
• 4. 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;8:62-72.
• 5. Serra E, Puig S, Otero D, Gaona A, Kruyer H, Ars E, et al. Confirmation of a double-hit model for the NF1 gene in benign neurofibromas. Am J Hum Genet 1997;61:512-9.
• 6. Swaiman KF, Ashwal S, Ferriero DM, Schor NF, Finkel RS, Gropman AL, et al. Swaiman’s Pediatric Neurology E-Book: Principles and Practice: Elsevier Health Sciences; 2017.
• 7. Ly KI, Blakeley JO. The Diagnosis and Management of Neurofibromatosis Type 1. Med Clin North Am 2019;103:1035-54.
• 8. Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers 2017;3:17004.
• 9. Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N, et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat 2000;15:541-55.
• 10. Ishida C, Gupta V. Genetics, Molecular Testing. StatPearls. Treasure Island (FL) 2021.
• 11. Ko JM, Sohn YB, Jeong SY, Kim HJ, Messiaen LM. Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofibromatosis type 1. Pediatr Neurol 2013;48:447-53.
• 12. Anderson S. Cafe au Lait Macules and Associated Genetic Syndromes. J Pediatr Health Care 2020;34:71-81.
• 13. Cassiman C, Legius E, Spileers W, Casteels I. Ophthalmological assessment of children with neurofibromatosis type 1. Eur J Pediatr 2013;172:1327-33.
• 14. Lubs ML, Bauer MS, Formas ME, Djokic B. Lisch nodules in neurofibromatosis type 1. N Engl J Med 1991;324:1264-6.
• 15. Maharaj A, Singh VR, Lalchan SA. Lisch and the Importance of His Nodules. West Indian Med J 2014;63:799-802.
• 16. Campen CJ, Gutmann DH. Optic Pathway Gliomas in Neurofibromatosis Type 1. J Child Neurol 2018;33:73-81.
• 17. Ostendorf AP, Gutmann DH, Weisenberg JL. Epilepsy in individuals with neurofibromatosis type 1. Epilepsia 2013;54:1810-4.
• 18. Serdaroglu E, Konuskan B, Karli Oguz K, Gurler G, Yalnizoglu D, Anlar B. Epilepsy in neurofibromatosis type 1: Diffuse cerebral dysfunction? Epilepsy Behav 2019;98:6-9.
• 19. Pozetti M, Belsuzarri TA, Belsuzarri NC, Seixas NB, Araujo JF. Neurofibromatosis type 1 and Chiari type 1 malformation: A case report and literature review of a rare association. Surg Neurol Int 2016;7:S469-72.
• 20. Roth J, Ber R, Constantini S. Neurofibromatosis Type 1-Related Hydrocephalus: Treatment Options and Considerations. World Neurosurg 2019;128:e664-e8.
• 21. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 2007;44:81-8.
• 22. Roy A, Barbarot S, Charbonnier V, Gayet-Delacroix M, Stalder JF, Roulin JL, et al. Examining the frontal subcortical brain vulnerability hypothesis in children with neurofibromatosis type 1: Are T2-weighted hyperintensities related to executive dysfunction? Neuropsychology 2015;29:473-84.
• 23. Blackburn J, Didi M, Avula S, Senniappan S. Isolated premature menarche in two siblings with Neurofibromatosis type 1. J Pediatr Endocrinol Metab 2020;33:813-6.
• 24. Soucy EA, van Oppen D, Nejedly NL, Gao F, Gutmann DH, Hollander AS. Height assessments in children with neurofibromatosis type 1. J Child Neurol 2013;28:303-7.