Alagille Syndrome and Aneurysmal Subarachnoid Hemorrhage

Abstract

The authors report the case of a 21-year-old female with a known history of Alagille syndrome (AGS) who was found to have a basilar terminus aneurysm without evidence of rupture. Prior to intervention, the patient’s hospital course became complicated by multiple medical problems associated with AGS. Subsequently, the patient had an acute neurological decline. An unenhanced CT of the head demonstrated diffuse subarachnoid hemorrhage, intraparenchymal hematoma and intraventricular hemorrhage. AGS is an autosomal dominant arteriodysplastic syndrome with multiple organ system involvement caused by a mutation in the Jagged1 gene. Intracranial hemorrhage is one of the many complications observed in this patient population. While there are multiple case reports in the literature reviewing the spectrum of cerebrovascular events and abnormalities, intracranial aneurysmal rupture has only recently been described. To our knowledge, this is the third reported case of documented aneurysmal subarachnoid hemorrhage in a patient with AGS. The authors present a brief review of the vascular abnormalities both intracranial and systemic seen in AGS. The genomic abnormalities of this syndrome are also reviewed with particular attention to the Jagged1 gene and the Notch receptor signaling pathway which may reveal elements of the pathophysiology involved in aneurysm formation and rupture in AGS patients. In light of the increased incidence of intracranial hemorrhage in AGS and the possible link to aneurysmal subarachnoid hemorrhage, establishing the incidence of intracranial aneurysms in AGS and the role of screening these patients is indicated.

Alagille syndrome case report: implications for forensic pathology and anthropology

“…However, while reviewing literature on Alagille syndrome, we came across a case report analogous to ours-the death of a child consequent to a large epidural hematoma suffered after minimal head trauma, which resulted also in the fracture of an "extremely thin, paper-like temporal bone" [36]. This study, together with ours, suggests that the problems in temporal bone thinness in Alagille syndrome are not just sporadic cases, but could represent a recurrent feature in these patients (especially since cases of fatal epidural hematoma in patients with Alagille syndrome are well reported [37], while their skull features are not). In our case, even though the temporal bone was the most altered in terms of mineralization and thickness, other bones appeared abnormally thin and paper like at autopsy.…”

“…In Alagille syndrome, however, death in the pediatric age range, secondary to intracranial bleeding after mild or no trauma, is common [37,41,42], since they tend also to have more vasculopathies than the normal population [41]. These range from stenosis of the internal carotid artery, intracerebral aneurysms, and non-atherosclerotic carotid artery anomalies to thin-walled vessels and moyamoya-like changes [42].…”

Pulmonary hemorrhage in children with Alagille syndrome undergoing cardiac catheterization

“…Hemorrhagic events, including both spontaneous bleeds and those associated with invasive procedures, are a well‐recognized cause of morbidity and mortality in children with AGS . However, little has been known about the incidence or severity of pulmonary hemorrhage in children with AGS undergoing cardiac catheterization.…”

“…Hemorrhagic complications during invasive procedures are common in children with Alagille syndrome (AGS) . Spontaneous bleeds, particularly intracranial bleeds, are also relatively common, and are thought to be a result of abnormalities in angiogenesis, hemostasis, and/or platelet function . This multisystemic bleeding tendency significantly contributes to morbidity and mortality in patients with AGS .…”

Liver Disease in the Adolescent

“…These bleeds respond well to surgical clip ligation. 38 Treatment of Alagille syndrome involves managing the different diseases in each affected organ system.…”