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：

---

患有 NF1 微缺失的儿童和青少年的临床特征。

 目的

据估计，1 型神经纤维瘤病 (NF1) 患者中有 5-11% 存在包含NF1基因及其侧翼区域的NF1微缺失。本研究的目的是评估患有NF1微缺失的儿童和青少年的临床表型。

 方法

我们回顾性分析了 30 名患有与外部可见神经纤维瘤相关的NF1微缺失的儿童和青少年。通过对 20 名NF1微缺失儿童和青少年进行全身磁共振成像 (MRI) 体积测定来确定内部肿瘤负荷。此外，还评估了整体发育迟缓、自闭症谱系障碍和注意力缺陷多动障碍（ADHD）的患病率。

 结果

与年龄匹配的基因内NF1突变患者相比，具有NF1微缺失的儿童和青少年更容易出现皮肤、皮下和外部可见的丛状神经纤维瘤。通过全身 MRI 分析，所有 20 名具有NF1微缺失的儿童和青少年均检测到内部神经纤维瘤。相比之下，28 名年龄匹配的无微缺失的 NF1 患者中，只有 17 名 (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。在接受调查的 30 名NF1微缺失儿童中，有 28 名（93%）观察到整体发育迟缓。我们的患者组的平均全面智商为 77.7，显着低于基因内NF1突变的患者。 17 名患有NF1微缺失的儿童和青少年中，有 15 名 (88%) 被诊断为 ADHD。此外，在接受调查的 24 名患者中，有 17 名 (71%) 的 T 分数≥ 60 至 75，表明有轻度至中度自闭症症状，因此NF1微缺失患者中出现这种症状的频率明显高于一般 NF1 人群。此外， NF1微缺失患者的平均总 T 分数显着高于一般 NF1 人群。

 结论

我们的研究结果表明， 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，需要专门的长期临床护理。