Congenital Horizontal Gaze Palsy, Progressive Scoliosis

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). See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/257