Mechanisms of Lethal Cerebrovascular Accidents in Turner Syndrome

Abstract

A case of intracerebral hemorrhage in Turner syndrome is reported with an analysis of possible causes of cerebrovascular accidents in this condition. A 42-year-old woman with known Turner syndrome died soon after hospital admission having been found unconscious at her home address. At autopsy, she showed typical features of Turner syndrome with short stature, webbing of the neck, underdeveloped breasts, and an increased carrying angle of the arm. Death was due to a large left-sided intracerebral hemorrhage extending from the left basal ganglia into the white matter of the frontal lobe and lateral ventricle. Cases of unexpected death in Turner syndrome may arise from occult cerebrovascular accidents which may be hemorrhagic or nonhemorrhagic. Associated features include hypertension, vascular malformations, accelerated atherogenesis, cystic medial necrosis, and moyamoya syndrome. The possibility of Turner syndrome should be considered in cases where there has been a lethal cerebrovascular event in a younger woman.

Hypertensive Cerebral Hemorrhage in a Patient with Turner Syndrome Caused by Deletion in the Short Arm of the X Chromosome

“…Its etiology is considered multifactorial, while possible mechanisms include high levels of plasma renin activity, obesity, aortic coarctation, and renal vascular abnormality [8,13,14]. In this report, the patient had untreated hypertension and associated cerebral hemorrhage, but her primary physician had not recognized hypertension during her routine visits.…”

A Case of Turner Syndrome Presenting as Aneurysmal Subarachnoid Hemorrhage

“…The arterial wall abnormalities in Turner syndrome are not restricted to the aorta. Arterial dilatation, enlargement, and increased intimal thickening, similar to those observed in the aorta, affect the cerebral arteries 1,6,7) . Theoretically, these underlying arterial wall abnormalities could lead to a higher risk of spontaneous aneurysm formation and rupture of the affected vessels in Turner syndrome 1,3,4) .…”

“…Arterial dilatation, enlargement, and increased intimal thickening, similar to those observed in the aorta, affect the cerebral arteries 1,6,7) . Theoretically, these underlying arterial wall abnormalities could lead to a higher risk of spontaneous aneurysm formation and rupture of the affected vessels in Turner syndrome 1,3,4) . Another explanation for cerebral aneurysms is that estrogen deficiency in patients with Turner syndrome may be hypothesized to contribute to intimal thickening, followed by outward remodeling and vessel enlargement.…”

“…The exact cause and underlying mechanism of aneurysm formation and the growth and development of SAH in Turner syndrome are unknown. It was most likely the rupture of dilated vessels stemming from vasculopathy, characterized by an arterial wall defect, increased intimal thickening, and enlarged arteries 1,7,8,11) . Connective tissue defects, such as cystic medial necrosis of the arterial wall, are common findings in postmortem examination of Turner syndrome with spontaneous artery dissection.…”

Pregnancy-associated aortopathy and sudden postpartum death

“…The age range for aortic dissection in pregnancy is 22 to 39 years with those at highest risk having an aortic root diameter of > 40 mm (as in the present case), a previous dissection and/or Marfan syndrome [ 3 , 4 ]. Additional risk factors include other connective tissue and genetic disorders such as Loeys-Dietz, Ehlers-Danlos, and Turner syndromes, anatomical anomalies such as bicuspid aortic valve and aortic coarctation, acute myocardial infarction, heavy smoking, obesity, and/or cocaine use [ 5 – 8 ]. A further group of familial aortopathies has been identified which are known as heritable thoracic aortic aneurysm and dissection (h-TAAD).…”