'Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome
'Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome
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DOI：
10.1212/wnl.0b013e3181c3fd12
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发表时间：
2009-12-01
期刊：
影响因子：
9.9
通讯作者：
Ronco, P.
中科院分区：
文献类型：
--
作者：
Alamowitch, S.;Plaisier, E.;Ronco, P.
背景：COL4A1 突变导致家族性孔脑畸形、婴儿偏瘫、脑小血管病 (CSVD) 和出血性中风。我们最近描述了 3 个具有密切局部 COL4A1 突变的家族的遗传性血管病伴肾病、动脉瘤和肌肉痉挛 (HANAC) 综合征。本研究的目的是描述 HANAC 的脑血管表型。方法：收集来自 3 个家庭的 14 名受影响受试者的详细临床数据。其中 9 例进行了 MRI 和磁共振血管造影 (MRA)。通过电子显微镜对 3 个家庭中受影响的受试者进行皮肤活检分析。结果：14 名受试者中只有 2 名出现临床脑血管症状：47 岁时发生轻微缺血性中风，48 岁时在抗凝治疗下发生少量外伤后出血。 MRI-MRA 显示 9 名研究对象中的 8 名（平均年龄 39.4 岁，21-57 岁）有脑血管病变，其中 6 名无症状。在 5 名患者中观察到独特的或多发性颅内动脉瘤，全部位于颈动脉虹吸管上。 7 名患者患有脑小血管病，其特征是白质变化 (7/7) 影响皮质下、脑室周围或脑桥区域、血管周围空间扩张 (5/7) 和腔隙性梗死 (4/7)。未观察到婴儿偏瘫、严重中风和孔脑畸形。皮肤活检显示真皮表皮交界处基底膜的改变与小动脉壁平滑血管细胞之间的细胞外基质扩张有关。结论：遗传性血管病伴肾病、动脉瘤和肌肉痉挛综合征的脑血管表型与脑小血管疾病和大血管疾病与颈动脉虹吸管动脉瘤相关。与家族性无脑畸形相比，这与出血性中风的易感性较低一致，表明与 COL4A1 突变相关的疾病的表型表达存在重要的临床异质性。神经病学（R）2009； 73：1873-1882
Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. The aim of this study was to describe the cerebrovascular phenotype of HANAC.Methods: Detailed clinical data were collected in 14 affected subjects from the 3 families. MRI and magnetic resonance angiography (MRA) were performed in 9 of them. Skin biopsies were analyzed by electron microscopy in affected subjects in the 3 families.Results: Only 2 of 14 subjects had clinical cerebrovascular symptoms: a minor ischemic stroke at age 47 years and a small posttraumatic hemorrhage under anticoagulants at age 48 years. MRI-MRA showed cerebrovascular lesions in 8 of 9 studied subjects (mean age 39.4 years, 21-57 years), asymptomatic in 6 of them. Unique or multiple intracranial aneurysms, all on the carotid siphon, were observed in 5 patients. Seven patients had a CSVD characterized by white matter changes (7/7) affecting subcortical, periventricular, or pontine regions, dilated perivascular spaces (5/7), and lacunar infarcts (4/7). Infantile hemiplegia, major stroke, and porencephaly were not observed. Skin biopsies showed alterations of basement membranes at the dermoepidermal junction associated with expansion of extracellular matrix between smooth vascular cells in the arteriolar wall.Conclusion: The cerebrovascular phenotype in hereditary angiopathy with nephropathy, aneurysm, and muscle cramps syndrome associates a cerebral small vessel disease and a large vessel disease with aneurysms of the carotid siphon. It is consistent with a lower susceptibility to hemorrhagic stroke than in familial porencephaly, suggesting an important clinical heterogeneity in the phenotypic expression of disorders related to COL4A1 mutations. Neurology (R) 2009; 73: 1873-1882