Kamath Binita M, Spinner Nancy B, Emerick Karan M, Chudley Albert E, Booth Carol, Piccoli David A, Krantz Ian D
Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, Pa 19104, USA.
Circulation. 2004 Mar 23;109(11):1354-8. doi: 10.1161/01.CIR.0000121361.01862.A4. Epub 2004 Mar 1.
Alagille syndrome (AGS) is a dominantly inherited multisystem disorder involving the liver, heart, eyes, face, and skeleton, caused by mutations in Jagged1. Intracranial bleeding is a recognized complication and cause of mortality in AGS. There are multiple case reports of intracranial vessel abnormalities and other vascular anomalies in AGS. The objective of this study was to characterize the nature and spectrum of vascular anomalies in AGS.
Retrospective chart review of 268 individuals with AGS was performed. Twenty-five patients (9%) had noncardiac vascular anomalies or events. Sixteen patients had documented structural vascular abnormalities. Two had basilar artery aneurysms, 7 had internal carotid artery anomalies, and another had a middle cerebral artery aneurysm. Moyamoya disease was described in 1 patient. Three of the 16 patients had aortic aneurysms, and 2 had aortic coarctations. One of the patients with a basilar artery aneurysm also had coarctation of the aorta. One of the individuals with an internal carotid artery anomaly also had renal artery stenosis. Nine more patients had intracranial events without documented vessel abnormalities. Vascular accidents accounted for 34% of the mortality in this cohort.
The vascular anomalies described in our cohort of AGS individuals identify an underrecognized and potentially devastating complication of this disorder. It is a major cause of morbidity and mortality in this population, accounting for 34% of the mortality. We have also reviewed the body of evidence supporting a role for Jagged1 and the Notch signaling pathway in vascular development.
阿拉吉列综合征（AGS）是一种由Jagged1基因突变引起的常染色体显性遗传的多系统疾病，累及肝脏、心脏、眼睛、面部和骨骼。颅内出血是AGS公认的并发症和死亡原因。有多个关于AGS颅内血管异常和其他血管畸形的病例报告。本研究的目的是描述AGS血管畸形的性质和范围。
对268例AGS患者进行回顾性病历审查。25例患者（9%）有非心脏血管畸形或事件。16例患者记录有结构性血管异常。2例有基底动脉动脉瘤，7例有颈内动脉异常，另1例有大脑中动脉动脉瘤。1例患者被诊断为烟雾病。16例患者中有3例有主动脉瘤，2例有主动脉缩窄。1例基底动脉动脉瘤患者同时有主动脉缩窄。1例颈内动脉异常患者同时有肾动脉狭窄。另外9例患者有颅内事件但未记录血管异常。血管意外占该队列死亡率的34%。
我们队列中AGS患者所描述的血管畸形表明该疾病存在一种未被充分认识且可能具有毁灭性的并发症。它是该人群发病和死亡的主要原因，占死亡率的34%。我们还回顾了支持Jagged1和Notch信号通路在血管发育中作用的证据。
