Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome

Davide Tonduti, Simona Orcesi, Emma M. Jenkinson, Imen Dorboz, Florence Renaldo, Celeste Panteghini, Gillian I. Rice, Marco Henneke, John H. Livingston, Monique Elmaleh, Lydie Burglen, Michèl A A P Willemsen, Luisa Chiapparini, Barbara Garavaglia, Diana Rodriguez, Odile Boespflug-Tanguy, Isabella Moroni, Yanick J. Crow

Research output: Contribution to journalArticle

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.

PATIENTS AND 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.

Original languageEnglish
Pages (from-to)604-10
Number of pages7
JournalEuropean Journal of Paediatric Neurology
Volume20
Issue number4
DOIs
Publication statusPublished - Jul 2016

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Aicardi Syndrome
Phenotype
Mutation
Cytomegalovirus Infections
Cysts
Differential Diagnosis
Leukoencephalopathy, Cystic, Without Megalencephaly
Inflammation
Infection
Genes

Keywords

  • Adolescent
  • Autoimmune Diseases of the Nervous System
  • Brain
  • Calcinosis
  • Child
  • Child, Preschool
  • Cysts
  • Cytomegalovirus Infections
  • Diagnosis, Differential
  • Female
  • Humans
  • Infant
  • Leukoencephalopathies
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Nervous System Malformations
  • Phenotype
  • Ribonucleases
  • Tomography, X-Ray Computed
  • Tumor Suppressor Proteins
  • Young Adult
  • Case Reports
  • Journal Article

Cite this

Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome. / Tonduti, Davide; Orcesi, Simona; Jenkinson, Emma M.; Dorboz, Imen; Renaldo, Florence; Panteghini, Celeste; Rice, Gillian I.; Henneke, Marco; Livingston, John H.; Elmaleh, Monique; Burglen, Lydie; Willemsen, Michèl A A P; Chiapparini, Luisa; Garavaglia, Barbara; Rodriguez, Diana; Boespflug-Tanguy, Odile; Moroni, Isabella; Crow, Yanick J.

In: European Journal of Paediatric Neurology, Vol. 20, No. 4, 07.2016, p. 604-10.

Research output: Contribution to journalArticle

Tonduti, D, Orcesi, S, Jenkinson, EM, Dorboz, I, Renaldo, F, Panteghini, C, Rice, GI, Henneke, M, Livingston, JH, Elmaleh, M, Burglen, L, Willemsen, MAAP, Chiapparini, L, Garavaglia, B, Rodriguez, D, Boespflug-Tanguy, O, Moroni, I & Crow, YJ 2016, 'Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome', European Journal of Paediatric Neurology, vol. 20, no. 4, pp. 604-10. https://doi.org/10.1016/j.ejpn.2016.03.009
Tonduti, Davide ; Orcesi, Simona ; Jenkinson, Emma M. ; Dorboz, Imen ; Renaldo, Florence ; Panteghini, Celeste ; Rice, Gillian I. ; Henneke, Marco ; Livingston, John H. ; Elmaleh, Monique ; Burglen, Lydie ; Willemsen, Michèl A A P ; Chiapparini, Luisa ; Garavaglia, Barbara ; Rodriguez, Diana ; Boespflug-Tanguy, Odile ; Moroni, Isabella ; Crow, Yanick J. / Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome. In: European Journal of Paediatric Neurology. 2016 ; Vol. 20, No. 4. pp. 604-10.
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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-Gouti{\`e}res 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.PATIENTS AND 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.",
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TY - JOUR

T1 - Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome

AU - Tonduti, Davide

AU - Orcesi, Simona

AU - Jenkinson, Emma M.

AU - Dorboz, Imen

AU - Renaldo, Florence

AU - Panteghini, Celeste

AU - Rice, Gillian I.

AU - Henneke, Marco

AU - Livingston, John H.

AU - Elmaleh, Monique

AU - Burglen, Lydie

AU - Willemsen, Michèl A A P

AU - Chiapparini, Luisa

AU - Garavaglia, Barbara

AU - Rodriguez, Diana

AU - Boespflug-Tanguy, Odile

AU - Moroni, Isabella

AU - Crow, Yanick J.

N1 - Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

PY - 2016/7

Y1 - 2016/7

N2 - 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.PATIENTS AND 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.

AB - 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.PATIENTS AND 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.

KW - Adolescent

KW - Autoimmune Diseases of the Nervous System

KW - Brain

KW - Calcinosis

KW - Child

KW - Child, Preschool

KW - Cysts

KW - Cytomegalovirus Infections

KW - Diagnosis, Differential

KW - Female

KW - Humans

KW - Infant

KW - Leukoencephalopathies

KW - Magnetic Resonance Imaging

KW - Male

KW - Mutation

KW - Nervous System Malformations

KW - Phenotype

KW - Ribonucleases

KW - Tomography, X-Ray Computed

KW - Tumor Suppressor Proteins

KW - Young Adult

KW - Case Reports

KW - Journal Article

U2 - 10.1016/j.ejpn.2016.03.009

DO - 10.1016/j.ejpn.2016.03.009

M3 - Article

C2 - 27091087

VL - 20

SP - 604

EP - 610

JO - European Journal of Paediatric Neurology

JF - European Journal of Paediatric Neurology

SN - 1090-3798

IS - 4

ER -