title: Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome.
abstract: BACKGROUND
  Cystic leukoencephalopathy without megalencephaly is a disorder related in some cases to RNASET2 mutations and characterized by bilateral anterior temporal subcortical cysts and multifocal lobar white matter lesions with sparing of central white matter structures. This phenotype significantly overlaps with the sequelae of in utero cytomegalovirus (CMV) infection, including the presence of intracranial calcification in some cases. Aicardi-Goutières syndrome (AGS) is another inherited leukodystrophy with cerebral calcification mimicking congenital infection. Clinical, radiological and biochemical criteria for the diagnosis of AGS have been established, although the breadth of phenotype associated with mutations in the AGS-related genes is much greater than previously envisaged.
  
  
  METHODS
  We describe the clinical, biochemical and radiological findings of five patients demonstrating a phenotype reminiscent of AGS.
  
  
  RESULTS
  All patients were found to carry biallelic mutations of RNASET2.
  
  
  CONCLUSIONS
  Our patients illustrate the clinical and radiological overlap that can be seen between RNASET2-related leukodystrophy and AGS in some cases. Our data highlight the need to include both disorders in the same differential diagnosis, and hint at possible shared pathomechanisms related to auto-inflammation which are worthy of further investigation.
authors.affiliation: Child Neurology Unit, IRCCS-Fondazione Istituto Neurologico Carlo Besta, Milan, Italy; Child Neurology and Psychiatry Unit, Department of Brain and Behavioural Sciences, University of Pavia, Italy. Electronic address: davidetondu@hotmail.com.
authors.forename: Davide
authors.initials: D
authors.lastname: Tonduti
authors.affiliation: Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Orcesi
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Jenkinson
authors.affiliation: PROTECT, INSERM U1141 Paris Diderot University, Sorbonne Paris Cité, France.
authors.forename: Imen
authors.initials: I
authors.lastname: Dorboz
authors.affiliation: AP-HP, Departement of Neuropediatrics and Metabolic Diseases, Robert Debré Hospital, Paris, France; AP-HP, Department of Child Neurology, Hôpital Armand-Trousseau, GHUEP, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Renaldo
authors.affiliation: Unit of Molecular Neurogenetics, Neurological Institute C. Besta Foundation IRCCS, Milan, Italy.
authors.forename: Celeste
authors.initials: C
authors.lastname: Panteghini
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.affiliation: University Medical Center, Department of Pediatrics and Adolescent Medicine, Georg August University, Göttingen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Henneke
authors.affiliation: Department of Paediatric Neurology, F Floor, Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, United Kingdom.
authors.forename: John H
authors.initials: JH
authors.lastname: Livingston
authors.affiliation: AP-HP, Department of Child Radiology, Robert Debré Hospital, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Elmaleh
authors.affiliation: AP-HP, Service de Génétique et d'Embryologie Médicale, Hôpital Armand Trousseau, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.affiliation: Department of Paediatric Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michèl A A P
authors.initials: MA
authors.lastname: Willemsen
authors.affiliation: Neuroradiology Unit, IRCCS-Fondazione Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Chiapparini
authors.affiliation: Unit of Molecular Neurogenetics, Neurological Institute C. Besta Foundation IRCCS, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.affiliation: PROTECT, INSERM U1141 Paris Diderot University, Sorbonne Paris Cité, France; AP-HP, Department of Child Neurology, Hôpital Armand-Trousseau, GHUEP, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.affiliation: PROTECT, INSERM U1141 Paris Diderot University, Sorbonne Paris Cité, France; AP-HP, Departement of Neuropediatrics and Metabolic Diseases, Robert Debré Hospital, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.affiliation: Child Neurology Unit, IRCCS-Fondazione Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Moroni
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom; INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Paris, France; Paris Descartes, Sorbonne Paris Cité University, Institute Imagine, Paris, France.
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
mesh_terms: D000293:Adolescent; D020274:Autoimmune Diseases of the Nervous System / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002114:Calcinosis / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D003560:Cysts / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D003586:Cytomegalovirus Infections / Q000151:congenital; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009421:Nervous System Malformations / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D012260:Ribonucleases / Q000235:genetics; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D025521:Tumor Suppressor Proteins; D012260:Ribonucleases; C425232:RNASET2 protein, human
keywords: Aicardi-Goutières syndrome; Calcification; Interferonopathy; Leukodystrophy; RNASET2