Compound Heterozygous Variants in ROBO1 Cause a Neurodevelopmental Disorder with Absence of Transverse Pontine Fibers and Thinning of the Anterior Commissure and Corpus Callosum

Publication date: Available online 2 February 2017
Source:Pediatric Neurology
Author(s): Sonia F. Calloni, Julie S. Cohen, Avner Meoded, Jane Juusola, Fabio M. Triulzi, Thierry A.G.M. Huisman, Andrea Poretti, Ali Fatemi
BACKGROUNDAxonal guidance disorders are a group of diseases characterized by white matter tracts with an anomalous course, failure to cross the midline, or presence of heterotopic white matter tracts. Diffusion tensor imaging (DTI) is a suitable non-invasive, in-vivo neuroimaging tool to study axonal guidance disorders. We report here on a novel disorder in a 9-year-old boy with compound heterozygous variants in the ROBO1 gene.PATIENT DESCRIPTIONThe child was referred to our hospital at the age of 13 months because of developmental delay. At the age of 9 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 and thinning of the anterior commissure and corpus callosum. DTI showed absence of the transverse pontine fibers and a thinning of both the anterior commissure and the corpus callosum. 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.CONCLUSIONIn our patient, the 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.



http://ift.tt/2jQIXDg