Sonia F Calloni1, Julie S Cohen2, Avner Meoded3, Jane Juusola4, Fabio M Triulzi5, Thierry A G M Huisman6, Andrea Poretti7, Ali Fatemi8. 1. 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; Università degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan, Italy. 2. Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland. 3. 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; Pediatric Radiology and Pediatric Neuroradiology, Johns Hopkins All Children's Hospital, St. Petersburg, Florida. 4. Whole Exome Sequencing Program, GeneDx, Gaithersburg, Maryland. 5. Department of Neuroradiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 6. 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. 7. 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. Electronic address: aporett1@jhmi.edu. 8. Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND: Axonal guidance disorders are characterized by white matter tracts with an anomalous course, failure to cross the midline, or presence of anomalous white matter tracts. Diffusion tensor imaging (DTI) is a suitable noninvasive, in vivo neuroimaging tool to study axonal guidance disorders. We describe a novel disorder in a boy with compound heterozygous variants in the ROBO1 gene. PATIENT DESCRIPTION: The child was referred at age 13 months because of developmental delay. At age nine years, he had severe intellectual disability and hyperactivity. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia. Brain magnetic resonance imaging with DTI revealed marked pontine hypoplasia, thinning of the anterior commissure and corpus callosum, and absence of the transverse pontine fibers. In addition, at the level of the pons the corticospinal tracts and medial lemnisci were not clearly separated from each other. Whole exome sequencing revealed compound heterozygous variants in the ROBO1 gene. CONCLUSION: This child's neuroimaging phenotype (absence of the transverse pontine fibers and thinning of the anterior commissure and corpus callosum as shown by DTI) is suggestive of an axonal guidance disorder and supports a pathogenic role of the compound heterozygous variants in the ROBO1 gene.
BACKGROUND: Axonal guidance disorders are characterized by white matter tracts with an anomalous course, failure to cross the midline, or presence of anomalous white matter tracts. Diffusion tensor imaging (DTI) is a suitable noninvasive, in vivo neuroimaging tool to study axonal guidance disorders. We describe a novel disorder in a boy with compound heterozygous variants in the ROBO1 gene. PATIENT DESCRIPTION: The child was referred at age 13 months because of developmental delay. At age nine years, he had severe intellectual disability and hyperactivity. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia. Brain magnetic resonance imaging with DTI revealed marked pontine hypoplasia, thinning of the anterior commissure and corpus callosum, and absence of the transverse pontine fibers. In addition, at the level of the pons the corticospinal tracts and medial lemnisci were not clearly separated from each other. Whole exome sequencing revealed compound heterozygous variants in the ROBO1 gene. CONCLUSION: This child's neuroimaging phenotype (absence of the transverse pontine fibers and thinning of the anterior commissure and corpus callosum as shown by DTI) is suggestive of an axonal guidance disorder and supports a pathogenic role of the compound heterozygous variants in the ROBO1 gene.
Authors: Filippo Arrigoni; Romina Romaniello; Denis Peruzzo; Andrea Poretti; Maria Teresa Bassi; Carlo Pierpaoli; Enza Maria Valente; Sara Nuovo; Eugen Boltshauser; Thierry André Gerard Marie Huisman; Fabio Triulzi; Renato Borgatti Journal: Eur Radiol Date: 2018-07-31 Impact factor: 5.315
Authors: Zineb Ammous; Lettie E Rawlins; Hannah Jones; Joseph S Leslie; Olivia Wenger; Ethan Scott; Jim Deline; Tom Herr; Rebecca Evans; Angela Scheid; Joanna Kennedy; Barry A Chioza; Ryan M Ames; Harold E Cross; Erik G Puffenberger; Lorna Harries; Emma L Baple; Andrew H Crosby Journal: PLoS Genet Date: 2021-09-27 Impact factor: 5.917