Elsevier

Legal Medicine

Volume 17, Issue 5, September 2015, Pages 309-312
Legal Medicine

Case report
Subarachnoid hemorrhage due to aneurysm rupture in a young woman with Alagille syndrome – A rare cause of sudden death

https://doi.org/10.1016/j.legalmed.2015.03.004Get rights and content

Highlights

  • The Alagille syndrome is a rare, autosomal dominant inherited disease which is mainly characterized by a reduction of the number of bile ducts leading to cholestasis.

  • Several other organs may be effected.

  • In the presented case a 25 year old woman with Alagille syndrome who had liver transplantation in the age of 7 and 8 years died suddenly and unexpectedly.

  • Cause of death was a subarachnoidal hemorrhage due to rupture of an undiagnosed aneurysm of the basilary artery.

  • Due to the high rate of vascular complications in patients with Alagille syndrome a vascular screening may be necessary.

Abstract

The Alagille syndrome (AGS) or arteriohepatic dysplasia is a rare, autosomal dominant inherited disease with a prevalence of approximately 1:100,000. AGS was first described in 1969 and affects liver, heart, arterial blood vessels, skeleton and the eyes. The expression of AGS is variable. In severe cases a liver transplantation is required. Presented is the case of a 25-year-old woman with AGS. At the age of 7 and 8 years she had liver transplantations. Other typical findings associated with Alagille syndrome (e.g. pulmonary or renal anomalies) were also present. The young woman apparently died suddenly and unexpectedly in a good health condition despite regular medical treatment. Cause of death was a subarachnoid hemorrhage with invasion of the hemorrhage into the ventricle system caused by a rupture of previously unknown large aneurysm in the terminal basilary artery. Intracranial vascular malformations are a common finding in patients with AGS and cause death in up to 16% of them.

Life expectancy in AGS patients depends on the severity of changes of the affected liver. But AGS is also responsible for various vascular abnormalities in several other organs which can cause lethal complications. Due to the high rate of vascular complications and intracranial hemorrhage with the leading cause of mortality in patients with AGS, vascular screening by the use of noninvasive imaging techniques (CT or MR angiography) is required to avoid unexpected sudden death.

Introduction

Alagille syndrome (AGS) or arteriohepatic dysplasia was first described by the French pediatrician Daniel Alagille in 1969 [1]. The prevalence of AGS has been reported as 1 in 100,000 live births [2]. AGS is an autosomal dominantly inherited disorder and it is mainly characterized by the reduction of the number of bile ducts leading to cholestasis and by multiple organ system involvement: cardiovascular system (peripheral pulmonary artery stenosis), eyes (posterior embryotoxon), skeleton (butterfly-like vertebral arch defects) and kidneys. It is associated with characteristic facial features with a small face, prominent forehead and hypertelorism of the deep set eyes [3], [4], [5]. An affection of the nervous and endocrine system has also been described [2], [3].

Intracranial vessel abnormalities and other vascular lesions are also present in AGS [6], [7], [8]. One case with lethal cerebral vascular lesion is presented.

Section snippets

Case report

A 25-year-old woman with AGS was unexpectedly found dead in her bed. At the age of 7 and 8 she had liver transplantations. Facial dysplasia, peripheral pulmonary artery stenosis (state following balloon dilatation and stent implantation) and vertebral anomalies as well as renal dysplasia were already diagnosed.

The young woman had been in a comparatively good health condition over the last few years and led a normal life. She consulted a doctor for routine diagnostic procedures regularly. 4 weeks

Discussion

AGS is the most common inherited disorder that causes liver disease in children caused by mutations of the JAG1 gene that encodes Jagged1 which is a ligand in the Notch receptor signaling pathway [9], [10], [11]. The Notch receptor is involved in the fetal development of various organs, which explains the multisystemic appearance. The receptor plays an important role in the organ and the vascular development [8], [9], [10]. Mutations are especially associated with an impaired development of the

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