Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, NiaoSong, Kaohsiung, 833, Taiwan.
Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, NiaoSong, Kaohsiung, 833, Taiwan.
BMC Neurol. 2020 Sep 1;20(1):329. doi: 10.1186/s12883-020-01910-1.
Primary familial brain calcification (PFBC) is a rare inherited disease characterized by multiple calcified foci in the brain parenchyma. MYORG is the first gene found to be associated with autosomal recessive PFBC. The precise pathogenic mechanism of neurodegeneration in PFBC remains unclear. The clinical phenotypes of PFBC are variable, and there is no clear correlation between clinical manifestations and radiological and pathological features of calcification.
Two sisters in a Taiwanese family presented with young-onset Parkinsonism and multifocal dystonia. Their brain CTs showed multiple intracerebral calcifications. The genetic study detected two heterozygous novel variants, c.104 T > A (p.Met35Lys) and c.850 T > C (p.Cys284Arg) in the MYORG gene. In both patients, MR susceptibility weighted images revealed calcification of the deep medullary veins. Tc ECD SPECT demonstrated a significant decrease of tracer uptake in the brain cortex and subcortical gray matter. Tc TRODAT-1 SPECT revealed decreased tracer uptake in the bilateral striatum.
Two novel MYORG variants were identified in Taiwanese family members presenting with PFBC. Abnormalities in the brain perfusion and dopamine transporter SPECTs suggest that cerebral ischemia due to extensive calcified vasculopathy, disruption of the basal ganglia-thalamo-cortical circuit, and nigrostriatal dopaminergic dysfunction are plausible pathogenic mechanisms of neurodegeneration in PFBC patients. Further investigation into the correlations between the pathogenicity-implicated imaging findings and the clinical phenotype are recommended.
原发性家族性脑钙化症（PFBC）是一种罕见的遗传性疾病，其特征是脑实质中有多个钙化灶。MYORG 是第一个被发现与常染色体隐性遗传 PFBC 相关的基因。PFBC 中神经退行性变的确切致病机制仍不清楚。PFBC 的临床表型多种多样，临床表现与钙化的影像学和病理学特征之间没有明确的相关性。
一个台湾家庭的两个姐妹表现为早发性帕金森病和多灶性肌张力障碍。她们的脑部 CT 显示多发性颅内钙化。基因研究检测到 MYORG 基因中的两个杂合新变异，c.104T > A（p.Met35Lys）和 c.850T > C（p.Cys284Arg）。在两名患者中，MR 磁敏感加权成像显示深部髓静脉钙化。Tc ECD SPECT 显示大脑皮质和皮质下灰质的示踪剂摄取显著减少。Tc TRODAT-1 SPECT 显示双侧纹状体的示踪剂摄取减少。
在台湾的家庭成员中发现了两个新的 MYORG 变异体。脑灌注和多巴胺转运体 SPECT 的异常提示广泛的钙化血管病引起的脑缺血、基底节-丘脑-皮质回路的破坏以及黑质纹状体多巴胺能功能障碍是 PFBC 患者神经退行性变的可能致病机制。建议进一步研究提示致病性的影像学发现与临床表型之间的相关性。
