title: RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection.
abstract: Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi-Goutières syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection.
  
  
  
  We reviewed a large-scale biorepository of patients with unsolved leukodystrophies and identified two individuals with required for meiotic nuclear division 1 (RMND1) mutations and similar magnetic resonance imaging (MRI) features, including temporal lobe cysts. Ten additional subjects with confirmed RMND1 mutations were identified as part of a separate disease specific cohort. Brain MRIs from all 12 individuals were reviewed for common neuroradiological features.
  
  
  
  MRI features in RMND1 mutations included temporal lobe swelling, with rarefaction and cystic evolution, enlarged tips of the temporal lobes, and multifocal subcortical white matter changes with confluent periatrial T2 signal hyperintensity. A combination of these features was present in ten of the 12 individuals reviewed.
  
  
  
  Despite the small number of reported individuals with RMND1 mutations, a clinically recognizable phenotype of leukoencephalopathy with temporal lobe swelling, rarefaction, and cystic changes has emerged in a subset of individuals. Careful clinical phenotyping, including for lactic acidosis, deafness, and severe muscle involvement seen in RMND1 mutation positive individuals, and MRI pattern recognition will be important in differentiating these patients from children with congenital infections like cytomegalovirus.
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ulrick
authors.affiliation: Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Amy
authors.initials: A
authors.lastname: Goldstein
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Cas
authors.initials: C
authors.lastname: Simons
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia; Illumina Inc, San Diego, California; School of Medicine and Health Sciences, The George Washington University, Washington, DC.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.
authors.forename: Guy
authors.initials: G
authors.lastname: Helman
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.
authors.forename: Amy
authors.initials: A
authors.lastname: Pizzino
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bloom
authors.affiliation: West Midlands Regional Genetics Service, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Vogt
authors.affiliation: Paediatric Neurology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Pysden
authors.affiliation: Muscular and Neurodegenerative Disorders Unit, Ospedale Pediatrico Bambino Gesu, Rome, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Diodato
authors.affiliation: Division of Metabolism, Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Martinelli
authors.affiliation: Temple Street Children's University Hospital, Dublin, Ireland.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Monavari
authors.affiliation: Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: Daniela
authors.initials: D
authors.lastname: Buhas
authors.affiliation: Department of Pediatrics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Clara D M
authors.initials: CD
authors.lastname: van Karnebeek
authors.affiliation: INSERM UMR 1141, DHU PROTECT, Paris Diderot University, Sorbonne Paris Cité, France.
authors.forename: Imen
authors.initials: I
authors.lastname: Dorboz
authors.affiliation: INSERM UMR 1141, DHU PROTECT, Paris Diderot University, Sorbonne Paris Cité, France; AP-HP, Department of Neuropediatrics and Metabolic Diseases, National Reference Center for Leukodystrophies, Robert Debré Hospital, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.affiliation: INSERM UMR 1141, DHU PROTECT, Paris Diderot University, Sorbonne Paris Cité, France; APHP, Department of Neuropediatrics, National Reference Center for Neurogenetic Disorders, Hôpital Armand-Trousseau, GHUEP, Paris, France; GRC ConCer-LD, Sorbonne Universités, UPMC Université Paris 06, Paris, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada; McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada.
authors.forename: Martine
authors.initials: M
authors.lastname: Tétreault
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada; McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada.
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.affiliation: Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Department of Pediatrics McGill University, Montreal, Quebec, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Bernard
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, UK.
authors.forename: Yi Shiau
authors.initials: YS
authors.lastname: Ng
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.affiliation: Department of Neurology, Children's National Medical Center, Washington, DC; Department of Integrated Systems Biology, George Washington University, Washington, DC; Department of Pediatrics, George Washington University, Washington, DC. Electronic address: avanderv@childrensnational.org.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
mesh_terms: D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003560:Cysts / Q000000981:diagnostic imaging; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics; D003638:Deafness / Q000000981:diagnostic imaging / Q000235:genetics*; D003937:Diagnosis, Differential; D006801:Humans; D007223:Infant; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D013702:Temporal Lobe / Q000000981:diagnostic imaging
chemical_list: D018797:Cell Cycle Proteins; C578871:RMND1 protein, human
keywords: MRI pattern recognition; RMND1; cytomegalovirus; genetics; leukoencephalopathy