Purpose

An estimated 5–11% of patients with neurofibromatosis type 1 (NF1) harbour NF1 microdeletions encompassing the NF1 gene and its flanking regions. The purpose of this study was to evaluate the clinical phenotype in children and adolescents with NF1 microdeletions.

Methods

We retrospectively analysed 30 children and adolescents with NF1 microdeletions pertaining to externally visible neurofibromas. The internal tumour load was determined by volumetry of whole-body magnetic resonance imaging (MRI) in 20 children and adolescents with NF1 microdeletions. Furthermore, the prevalence of global developmental delay, autism spectrum disorder and attention deficit hyperactivity disorder (ADHD) were evaluated.

Results

Children and adolescents with NF1 microdeletions had significantly more often cutaneous, subcutaneous and externally visible plexiform neurofibromas than age-matched patients with intragenic NF1 mutations. Internal neurofibromas were detected in all 20 children and adolescents with NF1 microdeletions analysed by whole-body MRI. By contrast, only 17 (61%) of 28 age-matched NF1 patients without microdeletions had internal tumours. The total internal tumour load was significantly higher in NF1 microdeletion patients than in NF1 patients without microdeletions. Global developmental delay was observed in 28 (93%) of 30 children with NF1 microdeletions investigated. The mean full-scale intelligence quotient in our patient group was 77.7 which is significantly lower than that of patients with intragenic NF1 mutations. ADHD was diagnosed in 15 (88%) of 17 children and adolescents with NF1 microdeletion. Furthermore, 17 (71%) of the 24 patients investigated had T-scores ≥ 60 up to 75, indicative of mild to moderate autistic symptoms, which are consequently significantly more frequent in patients with NF1 microdeletions than in the general NF1 population. Also, the mean total T-score was significantly higher in patients with NF1 microdeletions than in the general NF1 population.

Conclusion

Our findings indicate that already at a very young age, NF1 microdeletions patients frequently exhibit a severe disease manifestation which requires specialized long-term clinical care.

中文翻译：

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NF1微缺失的儿童和青少年的临床特征。

目的

估计有5-11％的1型神经纤维瘤病（NF1）患者携带包含NF1基因及其侧翼区域的NF1微缺失。这项研究的目的是评估儿童和青少年NF1微缺失的临床表型。

方法

我们回顾性分析了与外部可见神经纤维瘤有关的NF1微缺失的30名儿童和青少年。通过对20例NF1微缺失的儿童和青少年进行全身磁共振成像（MRI）定量测定内部肿瘤负荷。此外，评估了全球发育迟缓，自闭症谱系障碍和注意缺陷多动障碍（ADHD）的患病率。

结果

与年龄内具有基因内NF1突变的患者相比，患有NF1微缺失的儿童和青少年的皮肤，皮下和外部可见的丛状神经纤维瘤的发生率明显更高。通过全身MRI分析，在所有20名儿童和青少年中检测到内部神经纤维瘤，并伴有NF1微缺失。相比之下，在28例无微缺失的年龄匹配NF1患者中，只有17例（61％）患有内部肿瘤。NF1微缺失患者的总内部肿瘤负荷显着高于无微缺失的NF1患者。在30名NF1儿童中，有28名（93％）观察到了全球发育延迟微删除进行了调查。我们患者组的平均全面智商为77.7，显着低于基因内NF1突变患者的智商。在17例NF1微缺失儿童和青少年中，有15例（88％）被诊断出多动症。此外，在所调查的24位患者中，有17位（71％）的T分数≥60至75，表明有轻度至中度的自闭症症状，因此，与一般NF1人群相比，患有NF1微缺失的患者明显更频繁。而且，NF1微缺失患者的平均总T分值显着高于一般NF1人群。

结论

我们的发现表明，NF1微缺失患者在很小的时候就经常表现出严重的疾病表现，需要长期的专业临床护理。