title: Familial acute necrotizing encephalopathy due to mutation in the RANBP2 gene.
abstract: BACKGROUND
  Acute necrotizing encephalopathy (ANE) is a rare and severe parainfectious central nervous system disease in which previously healthy children develop rapidly progressive coma following viral illness. While most ANE are sporadic, familial autosomal dominant ANE due to mutations in the RANBP2 gene has been recently reported (ANE1 or infection-induced acute encephalopathy-3 (IIAE3)). To date, only few IIAE3 families with ADANE episodes have been described.
  
  
  OBJECTIVE
  To report a new family with ADANE, describe clinical and radiological features and discuss differential diagnosis including Leigh syndrome or multiple sclerosis.
  
  
  METHODS
  The family included 3 symptomatic individuals and one 59 year-old asymptomatic obligate carrier. Patients presented acute episodes of encephalopathy few days after common viral infection. Ages of onset ranged from 6 months to 5 years. Episodes not only occurred in childhood but also recurred in adulthood. Initial neurological signs included coma, focal neurological deficits and seizures. MRI showed typical necrotizing lesions primarily in the thalamus and brainstem, and in the temporal lobes and insula. CSF cell count and cultures were normal during episodes. RANBP2 gene screening identified pathogenic heterozygous c.1754C>T mutation (p.Thr585Met). Episodes led to cognitive or physical handicap in 2 patients and were fatal in one child.
  
  
  CONCLUSIONS
  IIAE3 or ADANE due to RANBP2 mutations has a large clinical heterogeneity. Our family illustrates the associated phenotypes from asymptomatic carrier to severe episodes of encephalopathy. Based on MRI features, the genetic IIAE3 diagnosis is important since prophylaxis and symptomatic management of infections may be beneficial, possibly in association with steroid or gammaglobulins.
authors.affiliation: Department of Neurology, Bicêtre Hospital, Assistance-Publique-Hôpitaux de Paris (AP-HP), France. Electronic address: christian.denier@bct.aphp.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Denier
authors.affiliation: Department of Pediatry, Bicêtre Hospital, Assistance-Publique-Hôpitaux de Paris (AP-HP), France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Balu
authors.affiliation: Department of Radiology, Bicêtre Hospital, Assistance-Publique-Hôpitaux de Paris (AP-HP), France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Husson
authors.affiliation: Department of Radiology, Bicêtre Hospital, Assistance-Publique-Hôpitaux de Paris (AP-HP), France.
authors.forename: Ghaidaa
authors.initials: G
authors.lastname: Nasser
authors.affiliation: Department of Genetics, Trousseau Hospital, AP-HP, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.affiliation: Department of Pediatry, Robert Debré Hospital, AP-HP, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.affiliation: Department of Neurology, Montpellier Hospital, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Labauge
authors.affiliation: Department of Neurology, Bicêtre Hospital, Assistance-Publique-Hôpitaux de Paris (AP-HP), France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chevret
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*
chemical_list: D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2
keywords: Acute necrotizing encephalopathy; IIAE3; Infection-induced acute encephalopathy-3; RANBP2