Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
PLoS Genet. 2021 May 5;17(5):e1009517. doi: 10.1371/journal.pgen.1009517. eCollection 2021 May.
Neurofibromatosis type-1 (NF1) patients suffer from cutaneous and subcutaneous neurofibromas (CNF) and large plexiform neurofibromas (PNF). Whole gene deletions of the NF1 gene can cause a more severe phenotype compared to smaller intragenic changes. Two distinct groups of NF1 whole gene deletions are type-1 deletions and atypical deletions. Our aim was to assess volumes and averaged annual growth-rates of CNF and PNF in patients with NF1 whole gene deletions and to compare these with NF1 patients without large deletions of the NF1 gene. We retrospectively evaluated 140 whole-body MR examinations of 38 patients with NF1 whole gene deletions (type-1 group: n = 27/atypical group n = 11) and an age- and sex matched collective of 38 NF1-patients. Age-dependent subgroups were created (0-18 vs >18 years). Sixty-four patients received follow-up MRI examinations (NF1whole gene deletion n = 32/control group n = 32). Whole-body tumor-volumes were semi-automatically assessed (MedX, V3.42). Tumor volumes and averaged annual growth-rates were compared. Median tumor-burden was significantly higher in the type-1 group (418ml; IQR 77 - 950ml, p = 0.012) but not in the atypical group (356ml;IQR 140-1190ml, p = 0.099) when compared to the controls (49ml; IQR 11-691ml). Averaged annual growth rates were significantly higher in both the type-1 group (14%/year; IQR 45-36%/year, p = 0.004) and atypical group (11%/year; IQR 5-23%/year, p = 0.014) compared to the controls (4%/year; IQR1-8%/year). Averaged annual growth rates were significantly higher in pediatric patients with type-1 deletions (21%/year) compared with adult patients (8%/year, p = 0.014) and also compared with pediatric patients without large deletions of the NF1 gene (3.3%/year, p = 0.0015). NF1 whole gene deletions cause a more severe phenotype of NF1 with higher tumor burden and higher growth-rates compared to NF1 patients without large deletions of the NF1 gene. In particular, pediatric patients with type-1 deletions display a pronounced tumor growth.
神经纤维瘤病 1 型（NF1）患者患有皮肤和皮下神经纤维瘤（CNF）和大型丛状神经纤维瘤（PNF）。NF1 基因的全基因缺失与较小的基因内变化相比，可能导致更严重的表型。NF1 全基因缺失有两种不同的类型：1 型缺失和非典型缺失。我们的目的是评估 NF1 全基因缺失患者的 CNF 和 PNF 体积和平均年增长率，并将其与 NF1 基因无大缺失的患者进行比较。我们回顾性评估了 38 例 NF1 全基因缺失患者（1 型组：n=27/非典型组：n=11）和 38 例年龄和性别匹配的 NF1 患者的 140 例全身磁共振检查。创建了年龄依赖的亚组（0-18 岁与>18 岁）。64 例患者接受了随访 MRI 检查（NF1 全基因缺失组 n=32/对照组 n=32）。使用 MedX（V3.42）半自动评估全身肿瘤体积。比较肿瘤体积和平均年增长率。1 型组的肿瘤负担中位数明显高于对照组（418ml；IQR 77-950ml，p=0.012），但非典型组（356ml；IQR 140-1190ml，p=0.099）则无显著差异。与对照组（49ml；IQR 11-691ml）相比，1 型组（14%/年；IQR 45-36%/年，p=0.004）和非典型组（11%/年；IQR 5-23%/年，p=0.014）的平均年增长率均显著更高。1 型组的儿童患者（21%/年）比成年患者（8%/年，p=0.014）和无 NF1 基因大缺失的儿童患者（3.3%/年，p=0.0015）的平均年增长率更高。与无 NF1 基因大缺失的 NF1 患者相比，NF1 全基因缺失导致 NF1 更严重的表型，肿瘤负担和生长率更高。特别是，1 型缺失的儿童患者表现出明显的肿瘤生长。
