Zhao Fen, Yue Xizan, Wang Guangyu, Zhang Hongwei
Department of Neurology, Children's Hospital Affiliated to Shandong University/Jinan Children's Hospital, Jinan, China.
Department of Neurosurgery, Children's Hospital Affiliated to Shandong University/Jinan Children's Hospital, Jinan, China.
Int J Dev Neurosci. 2025 Aug;85(5):e70038. doi: 10.1002/jdn.70038.
Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome. NF1-related vasculopathy represents a clinically significant yet underrecognized complication. Moyamoya syndrome, a rare cerebrovascular manifestation of NF1, has been rarely reported in the paediatric population. Epilepsy and hydrocephalus are also uncommon neurological manifestations of NF1. However, the co-occurrence of the above three symptoms in NF1 cases is rarely found.
Here, we report a 2-year-old boy with moyamoya syndrome, epilepsy and hydrocephalus caused by de novo NF1 pathogenetic variants.
He experienced a 1-week history of paroxysmal hands weakness and frequent seizures. Physical examination showed macrocephaly (head circumference was 52 cm), reduced distal muscle strength in both upper limbs (grade III) and the presence of 6 or more café-au-lait macules (CALMs). Brain magnetic resonance imaging (MRI) showed moyamoya syndrome and hydrocephalus. Electroencephalographic (EEG) monitored two episodes of electrical persistent seizures and one focal motor seizure. Trio whole exome sequencing (Trio-WES) demonstrated a de novo and heterozygous NF1 missense mutation (c.5488C > G, p. Arg1830Gly). The final diagnoses were 'neurofibromatosis type 1, moyamoya syndrome, epilepsy, and hydrocephalus'. Following surgical intervention and treatment with levetiracetam, the patient achieved normal muscle strength and was seizure-free.
When articles about complications of NF1 are placed in a separate category, little is written about NF-1-related moyamoya syndrome, hydrocephalus and epilepsy simultaneously. This report describes a case of NF1 with moyamoya syndrome combined with hydrocephalus and epilepsy, which could enhance clinicians' understanding of the neurological manifestations of NF1 and provide reference value for clinical practice.
1型神经纤维瘤病（NF1）是一种常染色体显性神经皮肤综合征。NF1相关血管病变是一种具有临床意义但未被充分认识的并发症。烟雾病综合征是NF1罕见的脑血管表现，在儿科人群中鲜有报道。癫痫和脑积水也是NF1不常见的神经表现。然而，在NF1病例中很少发现上述三种症状同时出现。
在此，我们报告一名2岁男孩，因新发NF1致病变异导致烟雾病综合征、癫痫和脑积水。
他有1周的阵发性手部无力和频繁癫痫发作史。体格检查显示巨头症（头围52厘米）、双上肢远端肌力减弱（III级）以及6个或更多的咖啡牛奶斑（CALMs）。脑部磁共振成像（MRI）显示烟雾病综合征和脑积水。脑电图（EEG）监测到两次持续性癫痫发作和一次局灶性运动性癫痫发作。三联体全外显子测序（Trio-WES）显示一个新发的杂合NF1错义突变（c.5488C＞G，p.Arg1830Gly）。最终诊断为“1型神经纤维瘤病、烟雾病综合征、癫痫和脑积水”。经过手术干预和左乙拉西坦治疗后，患者肌力恢复正常且无癫痫发作。
当关于NF1并发症的文章单独分类时，很少有关于NF-1相关烟雾病综合征、脑积水和癫痫同时出现的报道。本报告描述了一例NF1合并烟雾病综合征、脑积水和癫痫的病例，可增强临床医生对NF1神经表现的认识，并为临床实践提供参考价值。
