Yektay Farahmand Maha, Wallenius Joel, Wasselius Johan, Gråhamn Olof, Puschmann Andreas, Ilinca Andreea
Division of Neurology, Department for Clinical Sciences Lund, Lund University, Lund, Sweden.
Department of Neurology, Skåne University Hospital, Inga Marie Nilssons Gata 47, 205 02, Malmö, Sweden.
J Neurol. 2025 Sep 14;272(9):632. doi: 10.1007/s00415-025-13344-1.
Bilateral basal ganglia calcifications (BGCs), if severe, are known hallmarks for idiopathic BGC disease (IBGC), but if milder, are often considered radiological findings of unknown significance. In previous studies, only a minority of patients with BGC had monogenic forms of IBGC.
We studied consecutive patients from a tertiary neurology clinic with bilateral BGCs of variable severity, and their families. We analyzed known IBGC genes, and an extended panel of genes linked to monogenic stroke and metabolic conditions. Clinical, radiological, and genetic data were collected, including vascular risk factors, cerebrovascular events, imaging findings (total calcification score, white matter hyperintensities, ischemic/hemorrhagic lesions), and relevant family history.
Twenty-four families with BGCs and neurological symptoms were analyzed. Disease-causing variants were identified in 14 families (58.3%). Eight patients had IBGC (variants in SLC20A2, PDGFB, MYORG), 4 had mitochondrial disease (MT-TL1), and 2 had monogenic vascular conditions (GAL, MAP3K6). Three variants were novel. BGC severity was highest in IBGC cases, while vascular and mitochondrial cases had milder calcifications. White matter hyperintensities were seen in 94.7% of cases and correlated highly with the total calcification score. Clinical vascular events had occurred in 41.7% cases. No monogenic cause was found in 10 patients, although many of these showed clinical or radiological features suggestive of monogenic disease.
Bilateral BGCs can occur in many neurogenetic disorders apart from IBGCs, and a broader genetic search increases the diagnostic yield. Patients with BGCs frequently had clinical cerebrovascular events, which emphasizes the role of cerebrovascular pathology in BGCs.
双侧基底节钙化（BGCs）若严重，则是特发性BGC病（IBGC）的典型特征，但若程度较轻，通常被视为意义不明的影像学表现。在以往研究中，仅有少数BGC患者患有单基因形式的IBGC。
我们研究了一家三级神经科诊所中连续的双侧BGC程度各异的患者及其家属。我们分析了已知的IBGC基因以及与单基因卒中及代谢性疾病相关的一组扩展基因。收集了临床、影像学和遗传学数据，包括血管危险因素、脑血管事件、影像学表现（总钙化评分、白质高信号、缺血性/出血性病变）以及相关家族史。
分析了24个有BGCs且伴有神经症状的家庭。在14个家庭（58.3%）中鉴定出致病变异。8例患者患有IBGC（SLC20A2、PDGFB、MYORG基因变异），4例患有线粒体疾病（MT-TL1基因变异），2例患有单基因血管疾病（GAL、MAP3K6基因变异）。3个变异为新发现的。IBGC病例中的BGC严重程度最高，而血管和线粒体疾病病例的钙化程度较轻。94.7%的病例出现白质高信号，且与总钙化评分高度相关。41.7%的病例发生了临床血管事件。10例患者未发现单基因病因，尽管其中许多患者表现出提示单基因疾病的临床或影像学特征。
除IBGC外，双侧BGCs还可发生于多种神经遗传性疾病中，更广泛的基因检测可提高诊断率。BGC患者常发生临床脑血管事件，这凸显了脑血管病理在BGCs中的作用。
