遗传性弥漫性脑白质病变合并球状轴索一家系临床和影像学特征分析

Analysis of clinical and neuroimaging features in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids

目的报道1个由集落刺激因子1受体（colony-stimulating factor 1 receptor，CSF1R）基因突变所致的遗传性弥漫性脑白质病变合并球状轴索（hereditary diffuse leukoencephalopathy with neuroaxonal spheroids，HDLS）家系，并分析先证者的临床和神经影像学特征。方法收集1个HDLS家系，对其先证者及家系中另外1例患者进行病史询问、体格检查、神经心理评估、MRI、碳11标记的匹兹堡复合物B（carbon11 labeled Pittsburgh complex-B，11C-PIB）PET检查及基因检测。结果该家系4代中共有3例患者。首发症状为淡漠、记忆力下降、行动迟缓，病程后期出现大小便失禁、癫痫、卧床。基因检测显示先证者5号染色体上CSF1R基因第18号外显子c.2381T〉C（p. I794T）错义突变。2例患者头颅DWI显示双侧侧脑室体旁、半卵圆中心区多发、斑片状高信号，呈持续性为其特征，且早期有胼胝体受累。结论双侧侧脑室体旁、半卵圆中心区多发、斑片状持续性DWI高信号，有助于HDLS早期诊断。

ObjectiveTo explore the clinical and neuroimaging features in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids （HDLS） caused by mutation of the colony stimulating factor 1 receptor gene （CSF1R）.MethodsThe proband and another patient from a HDLS pedigree were assessed respectively through standardized clinical evaluation （medical history inquiry, physical examination）, neuropsychology assessment, MRI, genetic sequencing, as well as brain PET imaging with carbon11-labelled Pittsburgh compound-B （11C-PIB） .ResultsA HDLS pedigree with three patients was recruited to this study. Apathy, memory decline, slow behavior were the first symptoms for two of the patients. Being bedridden, urinary incontinence and epilepsy were developed at the later stage. A missense mutation c.2381T〉C （p. I794T） in exon 18 of the CSF1R gene of chromosome 5 was identified in the proband. The brain DWI illustrated multiple patchy high signal in periventricular white matter and centrum semiovale which was characterized by persistence, and the corpus callosum was affected in the early stage.ConclusionThe multiple patchy high signal with persistence in periventricular white matter and centrum semiovale of DWI is helpful for the early diagnosis of HDLS.