Abstract TP280: Monogenetic Stroke Syndrome Testing in Adults: A Single Center Experience

Abstract

As access and coverage of genetic testing has increased, it is being used more commonly in adults with strokes. However, no clear guidelines exist for who should undergo genetic testing. Our retrospective review aims to provide guidance in this regard and show our experience. Genetic testing was ordered at our comprehensive stroke center between June 2022 and September 2023. Tests were ordered from GeneDx and genetic material was collected by buccal swab after consent was obtained. Most of the testing was done routinely in the outpatient setting, but was rarely performed inpatient when diagnosis would change acute management. Genetic testing was ordered for 41 patients. Tests ordered included whole exome sequencing, mitochondrial genome sequencing, Marfan syndrome and thoracic aortic aneurysm and dissection panel, Disorders of connective tissues panel and expedited whole genome sequencing. Indications for testing included evaluation of carotid and vertebral dissections, recurrent stroke, cryptogenic stroke, and leukoencephalopathy. The average age of tested patients was 47. Of these patients, 6 had not had a stroke and the testing was ordered to evaluate etiology of vertebral or carotid dissections. Of the 35 patients being evaluated for stroke etiology, 60% had at least one stroke or TIA prior to presentation. Of patients tested, 14 had evidence of dissection in the carotid arteries or vertebral arteries. At the time of analysis, 27 patients had results available, of which 15 had negative results. Positive results with pathogenic variant were seen in 4 patients. Pathologic variants detected included mutations in ABCC6, NOTCH3, MT-TL1, HBB, and MCCACHC genes. Variants of unknown significance were seen in 8 patients. These variants included mutations in MYLK, COL5A1, COL5A2, KRIT1, CCM2, XPR1, MT-CYB, MT-ND4, and MT-ATP6 genes. This study highlights that in the right clinical population, like young patients with recurrent stroke, genetic testing can be helpful to elucidate the etiology of cerebrovascular disease when standard stroke work up is inconclusive. With retrospective review, we aim to provide guidance on indications for genetic testing in adults with stroke and dissection.