Nörofibromatozis tip 1 olan çocuklarda klinik fenotipi etkileyen faktörler

Yıl 2021, Cilt: 46 Sayı: 2, 646 - 653, 30.06.2021

Şule Çalışkan Kamış Begül Yağcı-küpeli

https://doi.org/10.17826/cumj.876942

Öz

Amaç: Bu çalışmada, Nörofibromatozis tip 1 (NF-1) tanısı ile izlenen çocukların klinik, radyolojik ve genetik özelliklerinin değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: Eylül 2012 ile Eylül 2019 tarihleri arasında Ulusal Sağlık Enstitüsü 1988 kriterlerine göre 0-18 yaş Nörofibramatozis tanısı almış hastalar çalışmaya dahil edildi. Hasta verileri, hasta dosyaları ve hastane bilgi sistemi üzerinden toplandı.
Bulgular: Toplam 50 hasta çalışmaya alındı. Erkek / kız oranı 0,92 idi. Tanı anındaki ortanca yaş 5,6 yıldı (yaş aralığı: 1-18 yıl). Tüm hastalarda saptanan en yaygın bulgu Cafe-au-lait lekeleriydi. Hastaların %60’ında aile öyküsü ve %14’ünde ebeveynler arasında akrabalık saptandı. Hastaların %12'sinde nörofibrom, %36'sında Lisch nodülü saptandı. Aksiler çillenme oranı %82, inguinal çillenme oranı %78 idi. Hastaların %22'sinde tümör, %12'sinde optik gliom ve %6'sında pleksiform nörofibrom saptandı. Kraniyal manyetik rezonans görüntülemede (MRG) %56 oranında fokal alanlarda sinyal yoğunluk artışı (FASI) saptandı.
Sonuç: NF-1'de mutasyon tipi ile klinik ve radyolojik özellikler arasındaki ilişki değerlendirildi. Mutasyonlu ve mutasyonsuz hastalar arasında klinik ve radyolojik bulgular açısından istatistiksel olarak anlamlı bir fark yoktu. NF-1 tanılı hastalarda klinik fenotipi belirleyen faktörleri ortaya çıkarmak için geniş ölçekli çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

Nörofibromatozis Tip 1, fenotip, cafe-au-lait lekeleri

Factors affecting clinical phenotype in children with neurofibromatosis type 1

Öz

Purpose: In this study, it was aimed to evaluate the clinical, radiological and genetic features of children who were followed up with the diagnosis of Neurofibromatosis type 1 (NF-1).
Materials and Methods: Patients who were 0-18 years diagnosed with Neurofibromatosis according to National Institute of Health 1988 criteria between September 2012 and September 2019 were included in the study. Patient data were collected through patient files and hospital information system.
Results: A total of 50 patients were included in the study. The male/female ratio was 0.92. The median age at the time of diagnosis was 5.6 years (age range: 1-18 years). The most common finding was cafe-au-lait spots detected in all patients. Family history was found in 60% of the patients and consanguinity between parents in 14%. Neurofibroma was detected in 12%, Lisch nodule in 36% of the patients. Axillary freckling ratio was 82%, inguinal freckling ratio was 78%. Tumors were found in 22% of the patients, optic glioma in 12%, and plexiform neurofibroma in 6%. Focal areas of signal intensity (FASI) was found 56% in cranial magnetic resonance imaging (MRI).
Conclusion: The relationship between mutation type and clinical and radiological features in NF-1 was evaluated. There was no statistically significant difference in clinical and radiological findings between patients with or without mutation. Large-scale studies are needed to reveal the factors that determine the clinical phenotype in patients with NF-1 diagnosis.

Anahtar Kelimeler

Neurofibromatosis Type 1, phenotype, cafe-au-lait spots

Kaynakça

• 1. Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook Of Pediatrics. 20th ed. Philadelphia PA: Elsevier; Chapter 596. Neurocutaneous Syndromes. 2016;2874–2876.
• 2. Brosius S. A History of von Recklinghausen's NF1, Journal of the History of the Neurosciences: Basic and Clinical Perspectives 2010;19(4):333-348.
• 3. Reynolds RM, Browning GGP, Nawroz I, Campbel IW. Von Recklinghausen’s Neurofibromatosis: Neurofibromatosis type 1. The Lancet 2003;361(9368):1552-1554.
• 4. Cimino PJ, Gutmann DH. Handbook of Clinical Neurology(eds DH Geschwind, HL Paulson, C Klein). Chapter 51. Neurofibromatosis type 1. 2018;799–811.
• 5. Leppävirta J, Kallionpää RA, Uusitalo E, Vahlberg T, Pöyhönen M, Peltonen J et al. Neurofibromatosis type 1 of the child increases birth weight. Am. J. Med. Genet. Part A, no. January, 2019;1–11.
• 6. Ly KI, Blakeley JO. The Diagnosis and Management of Neurofibromatosis Type 1. Medical Clinics of North America, 2019;103(6):1035–1054.
• 7. DeBella K, Szudek J, Friedman JM. Use of the National Institutes of Health Criteria for Diagnosis of Neurofibromatosis 1 in Children. Pediatrics. 2000;105(3):608–614.
• 8. Savar A, Cestari DM. Neurofibromatosis Type I: Genetics and Clinical Manifestations. Seminars in Ophthalmology. 2008;23(1):45–51.
• 9. Ramanjam V, Adnams C, Ndondo A, Fieggen G, Fieggen K, Wilmshurst J. Clinical Phenotype of South African Children With Neurofibromatosis 1. Journal of Child Neurology. 2006;21(1):63–70.
• 10. McKeever K, Shepherd CW, Crawford H, Morrison PJ. An epidemiological, clinical and genetic survey of neurofibromatosis type 1 in children under sixteen years of age. Ulster Med. J. 2008;77(3):160–163.
• 11. Korf BR. Review Article : Clinical Features and Pathobiology of Neurofibromatosis 1. Journal of Child Neurology. 2002;17(8):573–577.
• 12. Huson SM, Harper PS, Compston DAS. (1988). Von recklinghausen neurofibromatosis. Brain. 1988;111(6):1355–1381.
• 13. Kayl AE, Moore BD. Behavioral phenotype of neurofibromatosis, type 1. Mental Retardation and Developmental Disabilities Research Reviews. 2000;6(2):117–124.
• 14. Mazzocco MMM. Math Learning Disability and Math LD Subtypes. Journal of Learning Disabilities. 2001;34(6):520–533.
• 15. Hyman SL, Arthur Shores E, North KN. Learning disabilities in children with neurofibromatosis type 1: subtypes, cognitive profile, and attention-deficit–hyperactivity disorder. Developmental Medicine & Child Neurology. 2006;48(12):973.
• 16. Salman MS, Hossain S, Alqublan L, Bunge M, Rozovsky K. Cerebellar radiological abnormalities in children with neurofibromatosis type 1 : part 1 - clinical and neuroimaging findings. 2018;5(14):1–12.
• 17. Varan A, Şen H, Aydın B, Yalçın B, Kutluk T, Akyüz C. Neurofibromatosis type 1 and malignancy in childhood. Clinical Genetics. 2015;89(3):341–345.
• 18. Lobbous M, Bernstock JD, Coffee E, Friedman GK, Metrock LK, Chagoya G et al. An update on neurofibromatosis type 1-associated gliomas. Cancers.2020;12,(1):114.
• 19. Taylor T, Jaspan T, Milano G, Gregson R, Parker T, Ritzmann T et al. Radiological classification of optic pathway gliomas: Experience of a modified functional classification system. The British Journal of Radiology. 2008;81(970):761–766.