Delaney Siobhan, O'Connor Ged, Reardon William, Murphy Stephen J X, Tierney Sean, Ryan Barbara M, Delaney Holly, Doherty Colin P, Guiney Michael, Brennan Paul, Tobin W Oliver, McCabe Dominick J H
Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating The National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland.
Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland.
Front Neurol. 2019 Jan 29;9:1194. doi: 10.3389/fneur.2018.01194. eCollection 2018.
Alagille syndrome (AGS) is an autosomal-dominant, multisystem disorder caused by mutations in the JAG1 gene. A 34-year-old man was referred to our service 10 years ago with focal seizures with impaired awareness and transient slurred speech. He had a 5-year history of intermittent left monocular low-flow retinopathy. He has a family history of AGS. General examination revealed mild hypertension, aortic regurgitation, and livedo reticularis. Neurological examination was normal. He had mild hyperlipidaemia and persistently-positive lupus anticoagulant consistent with primary anti-phospholipid syndrome. Color Doppler ultrasound revealed low velocity flow in a narrowed extracranial left internal carotid artery (ICA). MR and CT angiography revealed a diffusely narrowed extracranial and intracranial left ICA. Formal cerebral angiography confirmed severe left ICA narrowing consistent with a left ICA "vasculopathy" and moyamoya phenomenon. Transthoracic echocardiogram revealed a bicuspid aortic valve and aortic incompetence. Molecular genetic analysis identified a missense mutation (A211P) in exon 4 of the JAG1 gene, consistent with AGS. AGS should be considered in young adults with TIAs/stroke and unexplained extracranial or intracranial vascular abnormalities, and/or moyamoya phenomenon, even in the absence of other typical phenotypic features. Gene panels should include JAG1 gene testing in similar patients.
阿拉吉列综合征（AGS）是一种常染色体显性多系统疾病，由JAG1基因突变引起。一名34岁男性于10年前因局灶性癫痫发作伴意识障碍和短暂性言语不清转诊至我院。他有5年间歇性左单眼低流量视网膜病变病史。他有AGS家族史。全身检查发现轻度高血压、主动脉瓣关闭不全和网状青斑。神经系统检查正常。他有轻度高脂血症，狼疮抗凝物持续阳性，符合原发性抗磷脂综合征。彩色多普勒超声显示左侧颅外颈内动脉（ICA）狭窄处血流速度降低。磁共振血管造影（MR）和计算机断层血管造影（CTA）显示左侧颅外和颅内ICA弥漫性狭窄。正式的脑血管造影证实左侧ICA严重狭窄，符合左侧ICA“血管病变”和烟雾病现象。经胸超声心动图显示二叶式主动脉瓣和主动脉瓣关闭不全。分子遗传学分析在JAG1基因第4外显子中鉴定出一个错义突变（A211P），符合AGS。对于有短暂性脑缺血发作（TIA）/中风且伴有无法解释的颅外或颅内血管异常和/或烟雾病现象的年轻人，即使没有其他典型的表型特征，也应考虑AGS。在类似患者的基因检测套餐中应包括JAG1基因检测。
