HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Data Supplement Data Supplement Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bosley, T. M. Articles by Baloh, R. W. Search for Related Content PubMed PubMed Citation Articles by Bosley, T. M. Articles by Baloh, R. W. Related Collections Ocular motility All Genetics

Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3

From the Neuro-ophthalmology Division (Dr. Bosley) and Pediatric Ophthalmology Division (D. Oystreck), King Khaled Eye Specialist Hospital, Riyadh; Department of Neurology (Dr. Salih), King Khalid University Hospital, Riyadh; Neurology Department (Drs. Jen and Baloh), UCLA Medical Center, Los Angeles, CA; Radiology Department (Dr. Lin), Johns Hopkins Hospitals, Baltimore, MD; Genetics Department (Dr. Abu-Amero), Neuroscience Department (Drs. Bosley, MacDonald, al Dhalaan, and Stigsby), and Surgery Department (Dr. al Zayed), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; and Neurology Department (Dr. Kansu), Hacettepe University Hospital, Ankara, Turkey.

Address correspondence and reprint requests to Dr. Thomas M. Bosley, King Khaled Eye Specialist Hospital, PO Box 7191, Riyadh 11462, Saudi Arabia; e-mail: tmbosley{at}bosleynet.net

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.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 12 issue to find the title link for this article.

J.C.J. and R.W.B. are supported by NIH grant DC05524.

Received July 13, 2004. Accepted in final form December 15, 2004.

This article has been cited by other articles:

				D. T. Oystreck, A. O. Khan, A. A. Vila-Coro, O. Oworu, N. Al-Tassan, W.-M. Chan, E. C. Engle, and T. M. Bosley Synergistic Divergence: A Distinct Ocular Motility Dysinnervation Pattern Invest. Ophthalmol. Vis. Sci., November 1, 2009; 50(11): 5213 - 5216. [Abstract] [Full Text] [PDF]

				P. Jissendi-Tchofo, D. Doherty, G. McGillivray, R. Hevner, D. Shaw, G. Ishak, R. Leventer, and A.J. Barkovich Pontine Tegmental Cap Dysplasia: MR Imaging and Diffusion Tensor Imaging Features of Impaired Axonal Navigation AJNR Am. J. Neuroradiol., January 1, 2009; 30(1): 113 - 119. [Abstract] [Full Text] [PDF]

				T. M. Bosley, M. A. Salih, I. A. Alorainy, D. T. Oystreck, M. Nester, K. K. Abu-Amero, M. A. Tischfield, and E. C. Engle Clinical characterization of the HOXA1 syndrome BSAS variant Neurology, September 18, 2007; 69(12): 1245 - 1253. [Abstract] [Full Text] [PDF]

				E. C. Engle Genetic Basis of Congenital Strabismus Arch Ophthalmol, February 1, 2007; 125(2): 189 - 195. [Abstract] [Full Text] [PDF]

				G Amoiridis, M Tzagournissakis, P Christodoulou, S Karampekios, H Latsoudis, T Panou, P Simos, and A Plaitakis Patients with horizontal gaze palsy and progressive scoliosis due to ROBO3 E319K mutation have both uncrossed and crossed central nervous system pathways and perform normally on neuropsychological testing J. Neurol. Neurosurg. Psychiatry, September 1, 2006; 77(9): 1047 - 1053. [Abstract] [Full Text] [PDF]

				W-M Chan, E I Traboulsi, B Arthur, N Friedman, C Andrews, and E C Engle Horizontal gaze palsy with progressive scoliosis can result from compound heterozygous mutations in ROBO3. J. Med. Genet., March 1, 2006; 43(3): e11 - e11. [Abstract] [Full Text] [PDF]