| Home | E-Submission | Sitemap | Contact Us |  
The Nerve > Volume 9(2); 2023 > Article
Ji and Hwang: A Case of Turner Syndrome Presenting as Aneurysmal Subarachnoid Hemorrhage


We report a rare case of cerebral aneurysmal subarachnoid hemorrhage (SAH) associated with Turner syndrome. A 34-year-old woman presented with aneurysmal SAH originating from a saccular aneurysm in the right anterior communicating artery. The patient underwent endovascular coil embolization of the aneurysm. The patient recovered favorably after surgery without any neurological deficits. She had previously been diagnosed with Turner syndrome, which was managed with medical treatment, including estrogen hormone replacement therapy. It is uncommon for a patient with Turner syndrome to present with aneurysmal SAH; nonetheless, aneurysmal SAH could be a clinical concern. Further investigations are needed to reveal the risk factors, vascular anatomy, and causative mechanisms of aneurysmal SAH in patients with Turner syndrome.


Turner syndrome is characterized by the absence of the X chromosome in all cells (45,XO genotype). These patients present with short stature, truncal obesity, gonadal dysgenesis, premature ovarian failure, and micrognathia. Half of these patients have aberrant vascular comorbidities, commonly involving the cardiovascular system3,5,7,9,10,13). However, vascular abnormalities of the neurovascular system presenting as potentially life-threatening complications are rare. Here, we present a rare case of subarachnoid hemorrhage (SAH) as a manifestation of cerebral aneurysm rupture in a patient with previously diagnosed Turner syndrome.


A 34-year-old right-handed woman presented with a sudden severe headache. She had a history of Turner syndrome for the last 20 years, which was managed with medical treatment, including estrogen hormone replacement therapy. Computed tomography revealed a SAH in the basal cistern (Fig. 1A). Routine cerebral angiography and 3-dimensional images demonstrated a saccular aneurysm of the right anterior communicating artery (Fig. 1B, C). The aneurysm was treated with endovascular coil embolization (Fig. 2). On admission, the patient underwent genetic analyses. One normal X chromosome was present in female cells, and the other sex chromosome was missing or structurally altered, compatible with Turner syndrome (Fig. 3). The patient recovered favorably without neurological deficits.


Turner syndrome is a chromosomal disorder that affects approximately 1 in 2,500 to 0 live births, is associated with a range of comorbidities involving the cardiovascular system, and affects both pediatric and adult patients. Vascular abnormalities, including aortic dilatation, dissection, and coarctation, are common in patients with Turner syndrome3,7,10,13,15,16). However, comorbidities involving the cerebrovascular system, such as cerebral aneurysms presenting with SAH are rare.
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 arteries1,7,8,11). 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. This finding is relatively common in cases of Turner syndrome complicated by histology 6,12). 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 arteries1,6,7). Theoretically, these underlying arterial wall abnormalities could lead to a higher risk of spontaneous aneurysm formation and rupture of the affected vessels in Turner syndrome1,3,4). 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. A growing body of evidence indicates a risk of aneurysm formation and SAH in women with estrogen loss, such as menopause5,7,11). Similar to all arteries, the cerebral arteries consist of three layers: the intima, media, and adventitia. The internal elastic lamina separates the intima from the media and is essentially a fenestrated elastin sheet. Collagen fibers are mainly produced by fibroblasts. Fibroblasts also produce, organize, and remove the extracellular matrix14). Collagen wasting, commonly observed in the bone and skin in the postmenopausal period due to decreased estrogen levels, could be responsible for the formation of aneurysms in the proximal segments of the cerebral arteries, as it occurs in various connective tissue diseases. Estrogen scavenges reactive oxygen species following endothelial injury and inhibits their formation11). Tightly regulated proteolytic degradation of the extracellular matrix is an important component of normal vascular homeostasis; however, if poorly controlled, it may contribute to the pathogenesis of cerebral aneurysms. Therefore, estrogen hormone replacement therapy may be an appropriate management strategy for early intervention in Turner syndrome to reduce the progression of intimal thickening and ultimately clinical atherosclerotic disease, although interventional studies are required to prove this point2,5,11,13). An other possible mechanism of cerebral aneurysms is the upregulation of transforming growth factor beta and matrix metalloproteinases, along with mutations in the gene loci for smooth muscle α-actin, which may also contribute to smooth muscle cell hyperproliferation in patients with Turner syndrome, resulting in vasculopathy of arterial wall defects, increased intimal thickening, and formation of aneurysm1,2,6,8,11). The incidence of hypertension and plasma renin activity is higher in Turner syndrome. The high plasma renin activity may be due to the renal vascular abnormalities of Turner syndrome. Therefore patients with Turner syndrome are susceptible to renovascular hypertension. Patients with Turner syndrome may develop vascular abnormalities in the renal and cerebral arteries due to chromosomal abnormalities. Both renovascular hypertension and cerebrovascular abnormalities may play a role in cerebrovascular incidents5,8,9).


Turner syndrome, associated with aneurysmal SAH, is a rare cerebrovascular anomaly. Our patient demonstrated the utility of genetic evaluation for patients with cerebrovascular disease and dysmorphism. Further investigations are needed to reveal the risk factors, vascular anatomy, and causative mechanisms of Turner syndrome with aneurysmal SAH.


No potential conflict of interest relevant to this article was reported.

Fig. 1.
(A) Computed tomography axial image demonstrating a diffuse subarachnoid hemorrhage in the basal cistern. (B, C) Routine and 3-dimensional preoperative right internal carotid artery angiography showing a typical saccular aneurysm of the anterior communicating artery.
Fig. 2.
(A, B) Routine and 3-dimensional post-embolization right internal carotid artery angiography demonstrating complete occlusion of the aneurysm sac of the anterior communicating artery.
Fig. 3.
Genetic findings. Turner syndrome is related to the X chromosome, which is 1 of the 2 sex chromosomes. It occurs when one normal X chromosome is present in a female's cells and the other sex chromosome is missing or structurally altered.


1. Byard RW: Mechanisms of lethal cerebrovascular accidents in turner syndrome. J Forensic Sci 61:842-844, 2016
crossref pmid
2. Carlson M, Silberbach M: Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature. J Med Genet 44:745-749, 2007
crossref pmid pmc
3. Finsterer J, Zartl M, Samec P: Spontaneous cerebral haemorrhage without hypertension in non-mosaic 45X Turner's syndrome. J Clin Neurosci 7:341-343, 2000
crossref pmid
4. Fuentes K, Silveira DC, Papamitsakis NI: Spontaneous carotid artery dissection in a patient with Turner syndrome. Cerebrovasc Dis 24:543-544, 2007
crossref pmid pdf
5. Gravholt CH, Juul S, Naeraa RW, Hansen J: Morbidity in Turner syndrome. J Clin Epidemiol 51:147-158, 1998
crossref pmid
6. Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, et al.: Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet 84:617-627, 2009
crossref pmid pmc
7. Manjila S, Miller BR, Rao-Frisch A, Otvos B, Mitchell A, Bambakidis NC, et al.: Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare cause of hemorrhagic stroke. J Stroke Cerebrovasc Dis 23:1242-1244, 2014
crossref pmid
8. Nathwani NC, Unwin R, Brook CG, Hindmarsh PC: The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome. Clin Endocrinol (Oxf) 52:371-377, 2000
crossref pmid pdf
9. Okamoto S, Morimoto Y, Reza MS, Kohso H, Ishikawa M, Takano M, et al.: Cerebral hemorrhage in turner syndrome: a case report. Clin Pediatr Endocrinol 14:35-37, 2005
crossref pmid pmc
10. Okuno S, Nishi N, Sakaki T: Putaminal hemorrhage in a case of Turner's syndrome with hyperaldosteronemia. No Shinkei Geka 33:171-176, 2005
11. Ostberg JE, Donald AE, Halcox JP, Storry C, McCarthy C, Conway GS: Vasculopathy in Turner syndrome: arterial dilatation and intimal thickening without endothelial dysfunction. J Clin Endocrinol Metab 90:5161-5166, 2005
crossref pmid
12. Preda SA, Predescu AM, Stoica LE, Albulescu DM, Ionovici N, Bugălă NM, et al.: Histopathological and immunohistochemical changes of the marginal periodontium in patients with Turner syndrome. Rom J Morphol Embryol 62:239-247, 2021
crossref pmid pmc
13. Ranke MB, Saenger P: Turner's syndrome. Lancet 358:309-314, 2001
14. Uitto J, Lichtenstein JR: Defects in the biochemistry of collagen in diseases of connective tissue. J Invest Dermatol 66:59-79, 1976
crossref pmid
15. Weinspach S, Siepermann M, Schaper J, Sarikaya-Seiwert S, Rieder H, Gerigk M, et al.: Intracranial hemorrhage in a female leading to the diagnosis of severe hemophilia A and Turner syndrome. Klin Padiatr 221:167-171, 2009
16. Yu MK, Jung MK, Kim KE, Kwon AR, Chae HW, Kim DH, et al.: Turner syndrome with spinal hemorrhage due to vascular malformation. Ann Pediatr Endocrinol Metab 20:235-237, 2015
crossref pmid pmc
Editorial Office
Department of Neurosurgery, Dankook University Hospital
201, Manghyang-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, South Korea
TEL: +0082-41-550-6280   FAX: +82-41-556-0524   
E-mail: spine1225@naver.com , mousehunt7@naver.com
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
Copyright © The Korean Society of Peripheral Nervous System.                 Developed in M2PI