title: Case of Small Vessel Disease Associated with COL4A1 Mutations following Trauma.
abstract: With this case report, we would like to heighten the awareness of clinicians about COL4A1 as a single-gene disorder causing cerebral small vessel disease and describe a previously unreported pathogenic missense substitution in COL4A1 (p.Gly990Val) and a new clinical presentation. We identified a heterozygous putatively pathogenic mutation of COL4A1 in a 50-year-old female with a history of congenital cataracts and glaucoma who presented with multiple diffusion-positive infarcts and areas of contrast enhancement following mild head trauma. We believe that this presentation of multiple areas of acute brain and vascular injury in the setting of mild head trauma is a new manifestation of this genetic disorder. Imaging findings of multiple acute infarcts and regions of contrast enhancement with associated asymptomatic old deep microhemorrhages and leukomalacia in adults after head trauma should raise a high suspicion for a COL4A1 genetic disorder. Radiographic patterns of significant leukoaraiosis and deep microhemorrhages can also be seen in patients with long-standing vasculopathy associated with hypertension, which our patient lacked. Our findings demonstrate the utility of genetic screening for COL4A1 mutations in young patients who have small vessel vasculopathy on brain imaging but who do not have significant cardiovascular risk factors.
authors.affiliation: Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Comprehensive Stroke Center at UC Neuroscience Institute, Ohio, USA.
authors.forename: Joao McONeil
authors.initials: JM
authors.lastname: Plancher
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital, Ohio, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hufnagel
authors.affiliation: Department of Radiology, University of Cincinnati College of Medicine, Neurotrauma Center at UC Neuroscience Institute, Cincinnati, Ohio, USA.
authors.forename: Achala
authors.initials: A
authors.lastname: Vagal
authors.affiliation: Division of Neurocritical Care, University of Cincinnati Health, Neurotrauma Center at UC Neuroscience Institute, Cincinnati, Ohio, USA.
authors.forename: Katrina
authors.initials: K
authors.lastname: Peariso
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital, Ohio, USA.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Saal
authors.affiliation: Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Comprehensive Stroke Center at UC Neuroscience Institute, Ohio, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
keywords: COL4A1; Cerebral small vessel disease; Heterozygous putatively pathogenic mutation