Vascular Anomalies in Alagille Syndrome

Authors:
  • NSNancy B. Spinner
    Nancy B. Spinner
  • KEKaran M. Emerick
    Karan M. Emerick
  • ACAlbert E. Chudley
    Albert E. Chudley
  • CBCarol Booth
    Carol Booth
  • DPDavid A. Piccoli
    David A. Piccoli
  • IKIan D. Krantz
    Ian D. Krantz
Publisher website
Google Scholar
Abstract
Background—Alagille syndrome (AGS) is a dominantly inherited multisystem disorder involving the liver, heart, eyes, face, and skeleton, caused by mutations inJagged1. 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.Methods and Results—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.Conclusions—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 forJagged1and the Notch signaling pathway in vascular development.

This publication has 26 references indexed in Scilit: