Evaluation of Clinical Findings and NF1 Genetic Variants in Patients Diagnosed with Neurofibromatosis Type 1: A Single-Center Experience

Öz

Objective: Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome with multisystemic involvement that facilitates tumour formation. The aim of this study was to evaluate the demographic and clinical characteristics as well as genetic results of pediatric patients diagnosed with neurofibromatosis type 1. Materials and Methods: This retrospective, cross-sectional descriptive study included 23 patients. Main disease criteria, clinical features, and genetic results obtained using next-generation sequencing and multiple-ligation probe amplification techniques were recorded. Information on zygosity, mutation types, variant positions, ACMG classification and inheritance models were analysed. Results: Café-au-lait spots were present in all patients. Inguinal/axillary freckling was the second most common finding seen in 60.9% of patients. Lisch nodules were observed in patients older than six years, whereas choroidal abnormalities were common in younger patients. Optic glioma was found in 13% of patients and cutaneous neurofibromas in 21.7% of patients, which is lower than that observed in adult patients. Focal signal intensity image was more common in patients with cognitive impairment (OR: 4.50, CI 95% 0.659-30.715, p=0.02). Epilepsy was diagnosed in two patients and treated with a single drug. Macrocephaly (30.4%) was the most common cranial deformity. Missense mutations (43.5%) were the most common, while one frameshift novel mutation (c.6771del. K2257Nfs*8) was identified. Conclusion: The emergence of new genetic technologies and advances in health care may facilitate earlier diagnosis of neurofibromatosis and the prediction and treatment of complications that may develop.

Anahtar Kelimeler

• Neurofibromatosis
• Variant
• FASI
• Rasopathy.

Destekleyen Kurum

None

Etik Beyan

This study was approved by Ethics committee of Samsun University Clinical Research (Approval number: GOKAEK/2024/12/6, Date: 01.07.2024).

Teşekkür

We would like to express our gratitude to all our colleagues who contributed to this study, as well as to our esteemed patients and their families.

Nörofibromatozis Tip 1 Tanılı Hastalarda Klinik Bulgular ve NF1 Genetik Varyantlarının Değerlendirilmesi: Tek Merkez Deneyimi

Öz

Amaç: Nörofibromatozis tip 1 (NF1), tümör oluşumunu kolaylaştıran multisistemik tutulumu olan yaygın bir nörokutanöz sendromdur. Bu çalışmanın amacı, nörofibromatozis tip 1 tanısı alan çocuk hastaların demografik ve klinik özelliklerinin yanı sıra genetik sonuçlarını değerlendirmektir. Gereç ve Yöntemler: Çalışmaya katılan toplam 23 hasta retrospektif olarak incelendi. Başlıca elde edilen sonuçlar analiz edildi. Buna zigosite, mutasyon tipleri, varyant pozisyonları, ACMG sınıflandırması ve kalıtım modellerine ilişkin bilgiler eklendi. Bu retrospektif, kesitsel tanımlayıcı çalışmaya 23 hasta dahil edildi. Hastalık ana kriterleri, klinik özellikleri, yeni nesil dizileme ve çoklu ligasyona bağlı prob amplifikasyon teknikleri kullanılarak elde edilen genetic sonuçları kaydedildi. Zigosite, mutasyon tipleri, varyant pozisyonları, ACMG sınıflandırması ve kalıtım modellerine ilişkin bilgiler analiz edildi. Bulgular: Café-au-lait lekeleri tüm hastalarda mevcuttu. Kasık/aksiller çillenme, hastaların %60,9'unda görülen ikinci en yaygın bulguydu. Lisch nodülleri altı yaşından büyük hastalarda gözlenirken, koroidal anormallikler daha küçük hastalarda yaygındı. Optik glioma hastaların %13'ünde, kutanöz nörofibromlar ise hastaların %21,7'sinde tespit edilmiş olup bu oran yetişkin hastalarda gözlenenden daha düşüktür. Bilişsel bozukluğu olan hastalarda fokal sinyal yoğunluğu görüntüsü daha yaygındı (OR: 4.50, CI 95 %0.659-30.715, p=0.02). İki hastada epilepsi tanısı konmuş ve tek bir ilaçla tedavi edilmiştir. Makrosefali (%30,4) en sık görülen kraniyal deformite idi. Missense mutasyonlar (%43,5) en sık görülürken, bir çerçeve kayması yeni mutasyon (c.6771del. K2257Nfs*8) tanımlanmıştır. Sonuç: Yeni genetik teknolojilerin ortaya çıkması ve sağlık hizmetlerindeki ilerlemeler nörofibromatozisin daha erken tanı almasını ve gelişebilecek komplikasyonların öngörülmesini ve tedavisini kolaylaştırabilir.

Anahtar Kelimeler

• Nörofibromatozis
• Varyant
• FASI
• Rasopati.

Etik Beyan

Çalışma için 26/06/2024 tarihinde Samsun Üniversitesi Girişimsel Olmayan Araştırmalar Etik Kurulu’ndan onay alınmıştır. Karar no:2024/12/6

Kaynakça

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