原发性家族性脑钙化(PFBC),也被称为Fahr病,根据神经影像学检查,是一种罕见的遗传性疾病,其特征是基底神经节的双侧钙化。其他大脑区域,比如丘脑,小脑,皮质下白质,也可能受到影响。在不同的临床表型中,最常见的表现是运动障碍,认知缺陷,和精神病。尽管PFBC患者总是表现出脑钙化,近三分之一的病例在临床上无症状.由于PFBC遗传学的进步,PFBC的诊断标准可能需要修改.到目前为止,七个基因与PFBC相关,包括四个显性遗传基因(SLC20A2,PDGFRB,PDGFB,和XPR1)和三个隐性遗传基因(MYORG,JAM2和CMPK2)。然而,大约50%的PFBC患者在这些基因中没有致病变异,和进一步的PFBC相关基因正在等待鉴定。目前已知基因的功能表明PFBC可能是由神经血管单元的功能障碍引起的,磷酸盐稳态的失调,或线粒体功能障碍。对PFBC潜在致病机制的进一步了解可能有助于新疗法的开发。
Primary familial brain calcification (PFBC), also known as Fahr\'s disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances. Although patients with PFBC always exhibit brain calcification, nearly one-third of cases remain clinically asymptomatic. Due to advances in the genetics of PFBC, the diagnostic criteria of PFBC may need to be modified. Hitherto, seven genes have been associated with PFBC, including four dominant inherited genes (SLC20A2, PDGFRB, PDGFB, and XPR1) and three recessive inherited genes (MYORG, JAM2, and CMPK2). Nevertheless, around 50% of patients with PFBC do not have pathogenic variants in these genes, and further PFBC-associated genes are waiting to be identified. The function of currently known genes suggests that PFBC could be caused by the dysfunction of the neurovascular unit, the dysregulation of phosphate homeostasis, or mitochondrial dysfunction. An improved understanding of the underlying pathogenic mechanisms for PFBC may facilitate the development of novel therapies.