title: Joubert syndrome: neuroimaging findings in 110 patients in correlation with cognitive function and genetic cause.
abstract: Joubert syndrome is a clinically and genetically heterogeneous ciliopathy. Neuroimaging findings have not been systematically evaluated in a large cohort of patients with Joubert syndrome in correlation with molecular genetic cause and cognitive function.
  
  
  
  Brain MRI of 110 patients with Joubert syndrome was included in this study. A comprehensive evaluation of brain MRI studies for infratentorial and supratentorial morphological abnormalities was performed. Genetic cause was identified by whole-exome sequencing, and cognitive functions were assessed with age-appropriate neurocognitive tests in a subset of patients.
  
  
  
  The cerebellar hemispheres were enlarged in 18% of the patients, mimicking macrocerebellum. The posterior fossa was enlarged in 42% of the patients, resembling Dandy-Walker malformation. Abnormalities of the brainstem, such as protuberance at the ventral contour of the midbrain, were present in 66% of the patients. Abnormalities of the supratentorial brain were present in approximately one-third of the patients, most commonly malrotation of the hippocampi. Mild ventriculomegaly, which typically did not require shunting, was present in 23% of the patients. No correlation between neuroimaging findings and molecular genetic cause was apparent. A novel predictor of outcome was identified; the more severe the degree of vermis hypoplasia, the worse the neurodevelopmental outcome was.
  
  
  
  The spectrum of neuroimaging findings in Joubert syndrome is wide. Neuroimaging does not predict the genetic cause, but may predict the neurodevelopmental outcome. A high degree of vermis hypoplasia correlates with worse neurodevelopmental outcome. This finding is important for prognostic counselling in Joubert syndrome.
authors.affiliation: Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Poretti
authors.affiliation: Intramural Research Program, Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Snow
authors.affiliation: Intramural Research Program, Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Summers
authors.affiliation: Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Aylin
authors.initials: A
authors.lastname: Tekes
authors.affiliation: Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Thierry A G M
authors.initials: TAGM
authors.lastname: Huisman
authors.affiliation: Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Nafi
authors.initials: N
authors.lastname: Aygun
authors.affiliation: Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.|Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Carson
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.|Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Doherty
authors.affiliation: Intellectual and Developmental Disabilities Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Parisi
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Maryland, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Toro
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Deniz
authors.initials: D
authors.lastname: Yildirimli
authors.affiliation: NIH Intramural Sequencing Center, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Meghana
authors.initials: M
authors.lastname: Vemulapalli
authors.affiliation: NIH Intramural Sequencing Center, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Jim C
authors.initials: JC
authors.lastname: Mullikin
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.|Department of Anatomy, Howard University College of Medicine, Washington District of Columbia, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Cullinane
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.|Inova Translational Medicine Institute, Falls Church, Virginia, USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Vilboux
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Maryland, USA.|Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.|Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.|Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.|Department of Pediatrics and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging* / Q000235:genetics / Q000523:psychology*; D002531:Cerebellum / Q000002:abnormalities* / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D015331:Cohort Studies; D005124:Eye Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics / Q000523:psychology*; D005260:Female; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000000981:diagnostic imaging* / Q000235:genetics / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D011379:Prognosis; D012160:Retina / Q000002:abnormalities* / Q000000981:diagnostic imaging; D000073359:Exome Sequencing
keywords: Cerebellar malformation; Ciliopathy; Cognition; Joubert syndrome; Magnetic resonance imaging