PP-35 Clinical features and therapeutic options in children with neurofibromatosis 1: a single centre experience

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Abstract

Background

Neurofibromatosis type 1 (NF1) is a genet-ic disorder that affects the growth and development of nerve cell tissue, with subsequent development of mul-tiple benign tumours of the nervous system and the skin, as well as the areas of abnormal skin colour and other clin-ical manifestations. Our study aimed to examine the in-cidence of clinical features and diagnostic parameters of NF1, as well as to identify the current therapeutic options.

Methods

We analysed retrospectively the medical doc-umentation of the patients of the Clinic of Neurology and Psychiatry for Children and Youth in Belgrade, in the peri-od from 2003–2016, fulfilling clinical diagnostic criteria for NF1. In addition to demographic data, the clinical mani-festations were obtained based on diagnostic criteria, ad-ditional clinical manifestations and supplementary diag-nostic tests. In statistical analysis, we used the methods of descriptive statistics, χ² and Mann-Whitney test. In order to identify the current treatment for the NF1, we analysed the recent pharmacological data, as well as the clinical tri-als registered in the ClinicalTrials.gov registry.

Results

The study group consisted of 65 patients (35 males/30 females) up to 18 years old at the first exam-ination. Multiple café au lait spots (patches of tan or light brown skin) were present in all patients (65, 100%). The frequency of axillary and inguinal freckles and Lisch nodules were 70.8% and 61.5%, respectively, while neu-rofibromas (cutaneous, subcutaneous and plexiform) were present in 66.2% of patients. Glioma optic pathway (GOP) was present in 13.2%, pathological findings of visu-al evoked potentials (VEP) were recorded in one third of patients, epilepsy with 10.8% and pathological electroen-cephalographic (EEG) patterns were described at 27.7% patients. Unidentified bright objects (UBO) on the MRI were described in 50.0% of patients, with no statistical dif-ferences regarding to the age of patients (p=0.635). Char-acteristic bone lesions were diagnosed in 27.7% patients, and positive family history was in 63.1%. Mental disorders and learning disabilities were diagnosed in 26.2% of patients. Furthermore, there was no correlation between the appearance of axillary/inguinal spots and Lisch nod-ules regarding to the age of patients (p=0.419; p=0.521, respectively); however, there was a statistically significant correlation between GOP and VEP (p=0.003). The current NF1 treatment includes the symptomatic therapy, includ-ing surgery and chemotherapy, while the specific treat-ment is not available yet. A total of 122 clinical trials were identified in the ClinicalTrials.gov registry; however, there are only few, phase 2, interventional studies in children: with mTOR inhibitors (sirolimus and everolimus) and RAS kinase inhibitor (tapifarnib).

Conclusion

NF1 is a multi-system disease that requires multidisciplinary approach and monitoring. The wide range of clinical features, inability to predict the severity of features/complications and limited therapeutic options make NF1 management a real clinical challenge. Future directions: to find therapeutic strategies or specific mol-ecule(s) to prevent/treat the harmful NF1 complications.

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