title: Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3.
abstract: OBJECTIVE
  To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on chromosome 11 and associated with defective decussation of certain brainstem neuronal systems.
  
  
  METHODS
  The authors examined 11 individuals with HGPPS from five genotyped families with HGPPS. Eight individuals had brain MRI, and six had electrophysiologic studies.
  
  
  RESULTS
  Horizontal gaze palsy was fully penetrant, present at birth, and total or almost total in all affected individuals. Convergence, ocular alignment, congenital nystagmus, and vertical smooth pursuit defects were variable between individuals. All patients developed progressive scoliosis during early childhood. All appropriately studied patients had hypoplasia of the pons and cerebellar peduncles with both anterior and posterior midline clefts of the pons and medulla and electrophysiologic evidence of ipsilateral corticospinal and dorsal column-medial lemniscus tract innervation. Heterozygotes were unaffected.
  
  
  CONCLUSIONS
  The major clinical characteristics of horizontal gaze palsy and progressive scoliosis were congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.
authors.affiliation: Neuro-ophthalmology Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. tmbosley@bosleynet.net
authors.forename: T M
authors.initials: TM
authors.lastname: Bosley
authors.forename: M A M
authors.initials: MA
authors.lastname: Salih
authors.forename: J C
authors.initials: JC
authors.lastname: Jen
authors.forename: D D M
authors.initials: DD
authors.lastname: Lin
authors.forename: D
authors.initials: D
authors.lastname: Oystreck
authors.forename: K K
authors.initials: KK
authors.lastname: Abu-Amero
authors.forename: D B
authors.initials: DB
authors.lastname: MacDonald
authors.forename: Z
authors.initials: Z
authors.lastname: al Zayed
authors.forename: H
authors.initials: H
authors.lastname: al Dhalaan
authors.forename: T
authors.initials: T
authors.lastname: Kansu
authors.forename: B
authors.initials: B
authors.lastname: Stigsby
authors.forename: R W
authors.initials: RW
authors.lastname: Baloh
mesh_terms: D000293:Adolescent; D000328:Adult; D001933:Brain Stem / Q000002:abnormalities / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009434:Neural Pathways / Q000002:abnormalities / Q000503:physiopathology; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D010375:Pedigree; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics*; D012600:Scoliosis / Q000235:genetics / Q000503:physiopathology*; D013577:Syndrome; D000097905:Roundabout Proteins
chemical_list: D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins