Congenital Horizontal Gaze Palsy

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Identifier 162-7
Title Congenital Horizontal Gaze Palsy
Ocular Movements Horizontal Gaze Palsy; Horizontal Vestibular Ocular Reflex Absent; Esotropia; Preservation of Convergence; Normal Vertical Gaze; Head Saccades
Creator Shirley H. Wray, M.D., Ph.D., FRCP, Professor of Neurology Harvard Medical School, Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Contributor Primary Shirley H. Wray, MD, PhD, FRCP, Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Subject Congenital Horizontal Gaze Palsy; Progressive Scoliosis; Mutation of the ROBO 3 Gene on Chromosome 11q23-q25; Congenital Cranial Disinnervation Syndrome; Mobius Syndrome
Supplementary Materials PowerPoint Presentation: Congenital Horizontal Gaze Palsy Progressive Scoliosis: Shirley H. Wray, M.D., Ph.D., FRCP Harvard Medical School
Presenting Symptom Inability to look to the side.
History The patient is an 8 year old boy with a rare autosomal recessive disorder characterized by congenital absence of conjugate horizontal eye movements preservation of vertical gaze and convergence and progressive scoliosis (HGPPS) developing in childhood. The child was referred to Dr. Cogan with a diagnosis of ocular motor apraxia, as he was using head saccades to look right and left. Ocular motility examination: Absent horizontal saccadic and pursuit eye movements Preservation of convergence Absent horizontal vestibular ocular reflex Esotropia of the left eye Normal vertical gaze Neurological examination was otherwise normal. Etiology: HGPPS is one of several genetic disorders of eye and lid control that are believed to result from cranial nuclear maldevelopment. Among these entities, the most closely related to HGPPS are Duane retraction syndrome and Mobius syndrome. Abnormal development of the abducens nucleus plays a crucial role in the pathogenesis of both these entities, as well as of HGPPS. These disorders, referred to as Congenital Cranial Disinnervation Syndrome, have the following features: • They are present at birth • Usually non-progressive • Have an autosomal inheritance pattern, that may occur sporadically. • May result from primary disinnervation, from failed or misguided development of neurons or • Result from aberrant innervation during development (i.e. secondary disinnervation). Brain MRI was not available in this case. Brain MRI in a 13 year old girl with HGPPS revealed: 1. A hypoplastic pons in which the posterior two-thirds were split into two halves by a midsagittal cleft extending ventrally from the fourth ventricular floor, generating a split pons sign on axial images. 2. The facial colliculi were absent, and the fourth ventricular floor was tent shaped. 3. The medulla was also hypoplastic and showed a butterfly configuration. 4. The inferior olivary nuclei were prominent with respect to the pyramids, and the prominence of the gracile and cuneate nuclei on the posterior aspect of the medulla was absent. MRI of the spine showed prominent scoliosis. (Figure 1A, B and C and Figure 2 Courtesy Andrea Rossi, M.D.) Pathogenesis of scoliosis: The pathogenesis of the scoliosis remains a subject of debate. When children with HGPPS undergo corrective surgery for scoliosis, the integrity of the spinal cord can be monitored by evoked potential studies. Because the descending cortical spinal tracts and the ascending somatosensory tracts normally decussate in the medulla, motor and sensory evoked potentials are monitored contralaterally. Surprisingly, HGPPS patients were found to have ipsilateral motor and sensory responses, suggesting that both these tracts were uncrossed. It is likely that the absence of normal decussation of these tracts on the ventral aspect of the hindbrain results in the midline medullary cleft seen by MRI in these patients. Scoliosis may result from lack of normal contralateral cross talk because of absence of crossing fibers, and suggests that scoliosis can, indeed, be neurogenic in etiology. What may be most interesting, however, is that HGPPS patients are otherwise asymptomatic, despite this extensive hindbrain and spinal cord miswiring, and suggests that these axons find their intended target, albeit on the ipsilateral rather than contralateral side. Pathogenesis of absent congenital horizontal gaze: The absence of horizontal gaze in these patients remains speculative, and may arise from aberrant supranuclear input onto the abducens motoneurons by axons from the pontine paramedian reticular formation that cannot cross the midline, and inability of the developing axons in the medial lateral fasciculus to cross the midline, and/or from lack of midline crossing by developing pontine neurons normally destined to cross. Head saccades: Children with congenital absence of conjugate horizontal eye movements may adopt several adaptive strategies to compensate for their deficit. They substitute rapid head movements (head saccades) for eye saccades to change gaze rapidly. When the head is restrained, they may use their intact vergence system to move both eyes into adduction and then cross-fixate, using the right eye to view objects seen on the left and vice versa. This strategy for looking to the right or left may also be used by patients with paralysis of horizontal gaze due to a pontine hemorrhage. (Review ID 923-5 Duane's Syndrome alongside this case).
Clinical This short video, made holding the boy's head, shows: Absent conjugate horizontal gaze Preservation of convergence Esotropia of the left eye He also had: Absent horizontal vestibular ocular reflex Normal vertical gaze Additional signs reported in this syndrome include: Horizontal, elliptical or pendular nystagmus Head shaking Intermittent slow blinking of one or both eyes Retraction of the non-fixing eye during vergence movements. Facial contraction with myokymia Progressive scoliosis which becomes disabling
Neuroimaging Neuroimaging studies were not obtained in this child. MRI Images obtained in a 13 year old girl with early onset thoracolumbar scoliosis. Figure 1A. Sagittal T1-weighted image of the brain shows depression of the floor of the fourth ventricle (arrowhead). The pons and medulla oblongata have a reduced volume. Figure 1B. Axial T2-weighted image at the level of the medulla oblongata shows rectangular configuration of the medulla. The floor of the fourth ventricle is tent shaped (arrows), with missing prominence of the cuneate and gracile nuclei. The inferior olivary nuclei (IO) are prominent with respect to the pyramids (P). Figure 1C. Axial T2-weighted image at the level of thye pons shows absence of the facial colliculi, with tent shaped configuration of the floor of the fourth ventricle (arrows). A deep midsagittal cleft extends ventrallY from the fourth ventricular floor, producing the split pons sign (arrowhead). Figure 2. MRI of the spine showing prominent scoliosis. Courtesy Andrea Rossi, M.D.
Anatomy Brainstem hypoplasia
Pathology Linkage studies have localized a mutation of the ROBO 3 gene on chromosome 11q23 -25 which is important for hindbrain midline axon crossing.
Etiology Genetic disorder Mutation of the ROBO 3 gene on chromosome 11q23-q25.
Disease/Diagnosis Congenital absence of conjugate horizontal eye movements and progressive scoliosis.
References 1. Bosley TM, Salih MA, Jen JC, Lin DD, Oystreck D, Abu-Amero KK, MacDonald DB, al Zayed Z, al Dhalaan H, Kansu T, Stigsby B, Baloh RW. Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3. Neurology. 2005;64:1196-1203. 2. Engle EC, Leigh RJ. Genes, brainstem development and eye movements. Neurology 2002;59:304-305. 3. Jen J, Coulin CJ, Bosley TM Salih MAM, Sabatti C, Nelson SF, Baloh RW. Familial horizontal gaze palsy with progressive scoliosis maps to chromosome 11q23-25. Neurology 2002;59:432-435. 4. Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rüb U, Shattuck D, Salamon G, Kudo LC, Ou J, Lin DD, Salih MA, Kansu T, Al Dhalaan H, Al Zayed Z, MacDonald DB, Stigsby B, Plaitakis A, Dretakis EK, Gottlob I, Pieh C, Traboulsi EI, Wang Q, Wang L, Andrews C, Yamada K, Demer JL, Karim S, Alger JR, Geschwind DH, Deller T, Sicotte NL, Nelson SF, Baloh RW, Engle EC. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science. 2004 Jun 4;304(5676):1509-1513. 5. Kruis JA, Houtman WA, Van Weerden TW. Congenital absence of conjugate horizontal eye movements. Doc Ophthalmol. 1987; 67:13-18. 6. Pieh C, Lengyel D, Neff A, Fretz C, Gottlob I. Brainstem hypoplasia in familial horizontal gaze palsy and scoliosis. Neurology. 2002;59:462-463. 7. Plaitakis A, Tzagournissakis M, Christodoulou P, Jen JC, Baloh RW. Vestibular modification of congenital pendular nystagmus in HGPPS with the ROBO3 mutation (abstract) Neurology 2005;64(suppl 1):A33. 8. Rossi A, Catala M, Biancheri R, Di Comite R, Tortori-Donati P. MR imaging of brain-stem hypoplasia in horizontal gaze palsy with progressive scoliosis. Am J Neuroradiol. 2004;25:1046-1048. 9. Sharpe JA, Silversides JL, Blair RD. Familial paralysis of horizontal gaze. Associated with pendular nystagmus, progressive scoliosis, and facial contraction with myokymia. Neurology 1975;25:1035-1040. 10. Sicotte NL, Plaitakas A, Salamon G, et al. Brainstem axon crossing defects in horizontal gaze palsy with progressive scoliosis assessed with diffusion tensor imaging and neurophysiological testing. Neurology 2005;64(Suppl1):A2. 11. Thomsen M, Steffen H, Sabo D, Niethard FU. Juvenile progressive scoliosis and congenital horizontal gaze palsy. J Pediatr Orthop B 1996;5:185-189. 12. Yee RD, Duffin RM, Baloh RW, Isenberg SJ. Familial congenital paralysis of horizontal gaze. Arch Ophthalmol. 1982;100:1449-1452. 13. Zweifach PH, Walton DS, Brown RH. Isolated congenital horizontal gaze paralysis. Occurrence of the near reflex and ocular retraction on attempted lateral gaze. Arch Ophthalmol 1969;81:345-350.
Relation is Part of 161-1, 169-29, 923-5
Contributor Secondary Ray Balhorn, Video Compressionist; Steve Smith, Videographer
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Date 1979
Type Image/MovingImage
Format video/mp4
Source 16 mm Film
Rights Management Copyright 2002. For further information regarding the rights to this collection, please visit:
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E, SLC, UT 84112-5890
Collection Neuro-ophthalmology Virtual Education Library: NOVEL
Language eng
ARK ark:/87278/s6wq31c9
Setname ehsl_novel_shw
Date Created 2007-03-08
Date Modified 2021-05-06
ID 188585
Reference URL
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