Objective: To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC). Methods: The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination. Results: Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time. Conclusions: The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.
目的： 探讨儿童伴钙化与囊变的脑白质病的临床特征及诊断依据。 方法： 对2012至2017年北京儿童医院诊治的4例伴钙化与囊变的脑白质病患儿的临床表现、辅助检查结果进行回顾性病例总结，并对其进行4个月至5年9个月的随访观察。 结果： 4例患儿中男、女各2例，发病年龄分别为2岁9月龄、6岁2月龄、7岁10月龄和5岁1月龄，临床表现主要有头痛、头晕、部分性癫痫发作及跛行，其中2例起病隐匿。4例患儿头颅影像学均显示脑内有多发钙化、囊变及脑白质病变，3例患儿磁敏感加权成像（SWI）显示脑内有多发微出血及钙化。1例脑组织活检病理显示皮层神经元减少，局部白质结构疏松，见多灶性淋巴细胞浸润、新鲜出血及胶质细胞增生；部分血管呈血管瘤样改变，管壁增厚、玻璃样变性、钙化，局灶管腔狭窄或闭塞。1例采用目标捕获二代测序法行SNORD118基因检测，发现复合杂合变异（n.*10G>A, n.82A>G），经家系验证，n.*10G>A来自父亲，是未见文献报道的新变异，n.82A>G来自母亲，为文献已报到的伴钙化与囊变的脑白质病的致病变异。随访研究显示2例已无明显症状，1例仍有癫痫发作，1例跛行症状减轻。 结论： 伴钙化与囊变的脑白质病常起病隐匿，临床症状缺乏特异性；头颅影像学所示的颅内钙化、囊变及脑白质病变三联征是诊断本病的必要条件，SWI所示脑内多发微出血是支持诊断的另一有力依据；病理资料难以早期获得，且为有创检查，非确诊的必需条件；基因诊断应作为确诊本病的金标准。.
Keywords: Calcifications; Child; Cysts; Leukoencephalopathies.