Nörofibromatozis tip 1 yeni tanı kriterlerine sahip çocukluk çağındaki hastaların klinik ve moleküler özellikleri

Burcu Yeter Doğan; Yasemin Kendir Demirkol

doi:10.19161/etd.1200311

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Nörofibromatozis tip 1 yeni tanı kriterlerine sahip çocukluk çağındaki hastaların klinik ve moleküler özellikleri

Öz

Amaç: Nörofibromatozis tip 1 cafe-au-lait makülleri, koltuk altı ve inguinal bölgelerde çillenme, Lisch nodülleri ve kutanöz veya pleksiform nörofibromlar ile karakterize sık görülen otozomal dominant kalıtımlı, nörokutanöz genetik bir hastalıktır. Son yıllarda Nörofibromatozis tip 1 yeni tanı kriterleri geliştirilmiş olup çalışmamızda bu güncellenen tanı kriterleri ile çocukluk çağındaki hastaların klinik ve moleküler özelliklerinin geriye dönük olarak değerlendirilmesi ve fenotip-genotip korelasyonu yapılması amaçlanmıştır. Gereç ve Yöntem: Nörofibromatozis tip 1 ön tanısı ile çocuk genetik polikliniğine başvuran ve NF1 geni dizi analizinde patojenik varyant saptanan pediatrik yaş grubundaki toplam 21 hastanın klinik ve moleküler bulguları retrospektif olarak incelenmiştir. Bulgular: Hastaların NF1 gen dizi analizleri sonucunda dokuz anlamsız, altı çerçeve kayması, beş kırpılma bölgesi varyantı ve bir de tüm gen delesyonu tespit edilmiştir. Bunlardan üçü ise daha önce bildirilmemiş yeni varyanttır. Hastaların hepsinde cafe-au-lait makülleri mevcut olup yaklaşık yarısında da koltuk altı ya da kasık bölgesinde çillenme vardı. 3 olguda cilt nörofibromu, 1 olguda ise Lisch nodülü gözlendi. Eski ve yeni tanı kriterleri karşılaştırıldığında hastaların 16’sı eski tanı kriterlerini karşılarken yeni tanı kriterlerine göre hastaların tamamı tanı almıştır. Sonuç: Yeni tanı kriterleri hastaların tanı alma oranını önemli derecede yükseltmiştir. Çalışmamızdaki hastaların tamamı yeni tanı kriterlerini karşılamıştır. Bu durum küçük yaşlarda tanı kriterlerini karşılamayan hastalarda NF1 moleküler analizinin önemini göstermektedir. Ayrıca bu çalışmayla daha önce tanımlanmamış üç yeni varyantla birlikte NF1 mutasyon spektrumunu genişlettik.

Anahtar Kelimeler

Clinical and molecular characteristics of pediatric patients with neurofibromatosis type 1 new diagnostic criteria

Abstract

Aim: Neurofibromatosis type 1 is a common autosomal dominant inherited neurocutaneous genetic disease characterized by cafe-au-lait macules, axillary and inguinal freckling, Lisch nodules, and cutaneous or plexiform neurofibromas. New diagnostic criteria for Neurofibromatosis type 1 have been developed in recent years. Our study aims to retrospectively evaluate childhood patients' clinical and molecular characteristics and make a phenotype-genotype correlation with these updated diagnostic criteria. Materials and Methods: The clinical and molecular findings of 21 patients in the pediatric age group who were admitted to the pediatric genetics outpatient clinic with a preliminary diagnosis of neurofibromatosis type 1 and who were also found to have a pathogenic variant in the NF1 gene sequence analysis were retrospectively analyzed. Results: As a result of the NF1 gene sequence analysis of the patients, nine nonsense, six frameshift, five splice site variants, and one whole gene deletion were detected. Three of these are novel variants that have not been reported before. All the patients had cafe-au-lait macules, and about half of them had freckles in the armpit or groin area. In addition, skin neurofibroma was observed in three cases, and Lisch nodule was observed in one case. When the old and new diagnostic criteria were compared, 16 of the patients met the old diagnostic criteria, while all the patients were diagnosed according to the new diagnostic criteria. Conclusion: The new diagnostic criteria have significantly increased the diagnosis rate of patients. All of the patients in our study met the new diagnostic criteria. This shows the importance of NF1 molecular analysis in patients who do not meet the diagnostic criteria at an early age. We also expanded the NF1 mutation spectrum with this study, with three new variants not previously identified.

Keywords

References

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Details

Primary Language

Turkish

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Burcu Yeter Doğan
0000-0002-6255-1057
Türkiye

Yasemin Kendir Demirkol ^*
0000-0001-8016-5224
Türkiye

Publication Date

March 19, 2024

Submission Date

November 15, 2022

Acceptance Date

August 25, 2023

Published in Issue

Year 2024 Volume: 63 Number: 1

DOI

https://doi.org/10.19161/etd.1200311

IZ

https://izlik.org/JA87KH88AW

Cite

RIS / Bibtex

Vancouver

1.Burcu Yeter Doğan, Yasemin Kendir Demirkol. Nörofibromatozis tip 1 yeni tanı kriterlerine sahip çocukluk çağındaki hastaların klinik ve moleküler özellikleri. EJM. 2024 Mar. 1;63(1):115-23. doi:10.19161/etd.1200311