title: A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13.
abstract: OBJECTIVE
  The detection of a leukoencephalopathy is a frequent situation in neurologic practice. In a number of cases, the etiology remains obscure despite extensive investigations. We characterized the clinical, pathologic, and genetic features of a novel hereditary vascular leukoencephalopathy.
  
  
  METHODS
  After the observation of a similar leukoencephalopathy in 2 sisters, clinical, neuroimaging, and molecular genetics investigations were conducted in 21 of their consenting relatives. Pathologic data were obtained in one patient.
  
  
  RESULTS
  Fourteen members presented with significant white matter lesions at MRI examination, among whom only 5 individuals were symptomatic. The main clinical manifestations included gait disturbances, transient movement disorders, stroke, and cognitive dysfunction. The 9 remaining members aged from 26 to 60 years were asymptomatic. The MRI pattern was highly stereotyped with symmetric white matter hyperintensities worsening with patient's age. We mapped the gene involved in this condition on chromosome 20q13. Neuropathologic examination suggested that this leukoencephalopathy is underlaid by a cerebral arteriolopathy affecting small preterminal arterioles, clearly distinct from amyloid angiopathy and hypertension-related small-vessel disease.
  
  
  CONCLUSIONS
  These data establish that this family is affected by a novel autosomal dominant vascular leukoencephalopathy mapping to chromosome 20q13. This disease is characterized by a progressive and age-related hemispheric and brainstem leukoencephalopathy contrasting with the paucity and late onset of clinical symptoms in most of the cases.
authors.affiliation: Service de Neurologie, Centre de Référence des Maladies Vasculaires Rares du Cerveau et de l'Oeil (CERVCO), AP-HP, Groupe Hospitalier Lariboisière-Saint-Louis, Paris, France. dominique.herve@lrb.aphp.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Hervé
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
authors.forename: Mélanie
authors.initials: M
authors.lastname: Rigal
authors.forename: Marie-Amelie
authors.initials: MA
authors.lastname: Dalloz
authors.forename: Aida
authors.initials: A
authors.lastname: Kawkabani Marchini
authors.forename: Jean
authors.initials: J
authors.lastname: De Lepeleire
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fontaine
authors.forename: Chantal
authors.initials: C
authors.lastname: Ceuterick-de Groote
authors.forename: Nassira
authors.initials: N
authors.lastname: Alili
authors.forename: Manuele
authors.initials: M
authors.lastname: Mine
authors.forename: Audrey
authors.initials: A
authors.lastname: Delaforge
authors.forename: Marie-Germaine
authors.initials: MG
authors.lastname: Bousser
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Guichard
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Françoise
authors.initials: F
authors.lastname: Gray
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Tournier-Lasserve
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D002890:Chromosomes, Human, Pair 20; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010375:Pedigree