Extracranial and Intracranial Vasculopathy With "Moyamoya Phenomenon" in Association With Alagille Syndrome.

Siobhan Delaney,Barbara M Ryan,Stephen J X Murphy,Colin P Doherty,Sean Tierney,Michael Guiney,W Oliver Tobin,Holly Delaney,Ged O'Connor,Paul Brennan,Dominick J H Mccabe,William Reardon

doi:10.3389/fneur.2018.01194

Abstract

Background: Alagille syndrome (AGS) is an autosomal-dominant, multisystem disorder caused by mutations in the JAG1 gene.Case Description: 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.Investigations: 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.Discussion: 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.

Highlights

Alagille syndrome is an autosomaldominant, multisystem disorder with a prevalence of 1 in 70,000 [1, 2], typically characterized by dysmorphic facial features, posterior embryotoxon, axial skeletal defects, peripheral pulmonary arterial hypoplasia, and intrahepatic cholestasis [3]
The stereotyped episodes of visual blurring and monocular oscillopsia were consistent with left ocular TIAs due to ipsilateral lowflow retinopathy associated with left CCA and severe left internal carotid artery (LICA) vasculopathy with Alagille syndrome (AGS)
It is reassuring that his cerebrovascular symptoms were controlled during medium-term follow up with active treatment of vascular risk factors and aspirin monotherapy, despite ongoing smoking

Summary

Background

Alagille syndrome (AGS) is an autosomal-dominant, multisystem disorder caused by mutations in the JAG1 gene. Case Description: 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. 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. Molecular genetic analysis identified a missense mutation (A211P) in exon 4 of the JAG1 gene, consistent with AGS

Discussion

INTRODUCTION

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ETHICS STATEMENT