Abstract 3828: Cerebrovascular Disease And Risk Of Stroke In Patients With ACTA2 R179H And R179L Mutations
Cerebrovascular disease and risk of stroke in patients with ACTA2 R179H and R179L mutations
Ellen S. Regalado1, John R. Østergaard2, Vijeya Ganesan3, Dong-chuan Guo1, and Dianna M. Milewicz1 1Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA; 2Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital, Skejby, Denmark; 3Neurosciences Unit, Institute of Child Health, University College London, London, UK Mutations in the ACTA2 gene, which codes for the smooth muscle specific isoform of alpha actin, predispose to a variety of vascular diseases, including thoracic aortic aneurysm and dissection, early onset stroke, and coronary artery disease. Recently we reported a severe de novo ACTA2 p.R179H mutation that causes a syndromic smooth muscle dysfunction resulting in aortic aneurysms, patent ductus arteriosus, fixed dilated pupils, hypotonic bladder, malrotation and hypoperistalsis of the gut, and pulmonary hypertension. Additionally, childhood onset of cerebrovascular disease is a prominent feature of this syndrome. To understand the extent of cerebrovascular disease and risk of stroke in these patients, we examined the clinical data of 9 patients recruited worldwide (8 Caucasians, 1 Asian; female to male ratio, 5:4; 8 with p.R179H mutation, 1 with p.R179L mutation). These patients ranged in age from 1 to 27 years old at the time of diagnosis of the ACTA2 mutation. All of these patients demonstrated multiple areas of narrowing of the intracranial vessels and increased T2 signal intensity in the periventricular white matter. Eight patients had bilateral stenosis of the distal internal carotid arteries and ectasia of the internal carotid arteries involving the petrous, cavernous and clinoidal segments and one patient had occlusion of the basilar artery only. Of these 9 patients, 5 have presented with ischemic stroke or recurrent transient ischemic attacks (age range, 2-27 years old; female to male ratio, 4:1), 4 of whom demonstrated cerebral infarction on MR imaging (age range, 2-16 years old). Two patients underwent bilateral revascularization procedures at age 9 and 6 years; the 9 year old patient developed an acute ischemic stroke within a year of surgery whereas the 6 year old remains stroke free 10 years after surgery. These data demonstrates the severity of cerebrovascular disease presentation in this subset of patients with the ACTA2 mutation and underlines the need for early diagnosis and careful surveillance and management in order to prevent ischemic strokes.
- © 2012 by American Heart Association, Inc.