Davide Tonduti1, Simona Orcesi2, Emma M Jenkinson3, Imen Dorboz4, Florence Renaldo5, Celeste Panteghini6, Gillian I Rice3, Marco Henneke7, John H Livingston8, Monique Elmaleh9, Lydie Burglen10, Michèl A A P Willemsen11, Luisa Chiapparini12, Barbara Garavaglia6, Diana Rodriguez13, Odile Boespflug-Tanguy14, Isabella Moroni15, Yanick J Crow16. 1. 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. 2. Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy. 3. 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. 4. PROTECT, INSERM U1141 Paris Diderot University, Sorbonne Paris Cité, France. 5. 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. 6. Unit of Molecular Neurogenetics, Neurological Institute C. Besta Foundation IRCCS, Milan, Italy. 7. University Medical Center, Department of Pediatrics and Adolescent Medicine, Georg August University, Göttingen, Germany. 8. Department of Paediatric Neurology, F Floor, Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, United Kingdom. 9. AP-HP, Department of Child Radiology, Robert Debré Hospital, Paris, France. 10. AP-HP, Service de Génétique et d'Embryologie Médicale, Hôpital Armand Trousseau, Paris, France. 11. Department of Paediatric Neurology, Radboud University Medical Center, Nijmegen, The Netherlands. 12. Neuroradiology Unit, IRCCS-Fondazione Istituto Neurologico Carlo Besta, Milan, Italy. 13. 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. 14. PROTECT, INSERM U1141 Paris Diderot University, Sorbonne Paris Cité, France; AP-HP, Departement of Neuropediatrics and Metabolic Diseases, Robert Debré Hospital, Paris, France. 15. Child Neurology Unit, IRCCS-Fondazione Istituto Neurologico Carlo Besta, Milan, Italy. 16. 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.
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.
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.
Authors: P Benjamin; S Sudhakar; F D'Arco; U Löbel; O Carney; C-J Roux; N Boddaert; C Hemingway; D Eleftheriou; K Mankad Journal: AJNR Am J Neuroradiol Date: 2021-12-23 Impact factor: 3.825
Authors: Zachary A Klase; Svetlana Khakhina; Adriano De Bernardi Schneider; Michael V Callahan; Jill Glasspool-Malone; Robert Malone Journal: PLoS Negl Trop Dis Date: 2016-08-25
Authors: Kerstin W Sinkevicius; Thomas R Morrison; Praveen Kulkarni; Martha K Caffrey Cagliostro; Sade Iriah; Samantha Malmberg; Julia Sabrick; Jennifer A Honeycutt; Kim L Askew; Malav Trivedi; Craig F Ferris Journal: Dis Model Mech Date: 2018-06-27 Impact factor: 5.758