Horizontal Gaze Palsy with Progressive Scoliosis

Dear Editor,

Horizontal gaze palsy with progressive scoliosis (HGPPS) is an exceedingly rare congenital disorder characterized by the absence of horizontal eye movements and the development of progressive scoliosis. With only a handful of cases reported globally, the scarcity of instances underscores the distinctive nature of this neurologic condition.

Here, we present a 12-year-old boy, a developmentally normal child born to nonconsanguineous parents, who presented with complaints of horizontal head nodding and inability to move eyeballs sideways, which were noticed when he was young. The child was able to look up and down without any difficulty. There was no history of drooping of eyelids or double vision, no history suggestive of diurnal variation or fluctuation, no history suggestive of other cranial nerve involvement, and no history of tremulousness in the limbs.

On examination, the child was conscious and oriented, small-amplitude sideways oscillations of the head were noted, and bilateral pendular nystagmus was present. Higher mental functions were normal. Cranial nerve examination revealed absent horizontal gaze, which was non-maneuverable with preserved vertical gaze [Figure 1]. Convergence was normal. Pupils were reacting well to light, and visual acuity and fundus were normal. Other cranial nerves were intact. There was no weakness of limbs and trunk, sensory system examination was normal, and there were no cerebellar signs. Spine examination revealed scoliosis of thoracolumbar region with concavity toward right. Other systemic examination was normal. With all these clinical features, the possibility of HGPPS was considered.

Figure 1.

Extraocular examination shows (a and c) preserved vertical gaze with (b) absent horizontal gaze

The child was evaluated, which revealed normal intelligence quotient. Ophthalmologic evaluation showed horizontal gaze palsy with normal visual acuity, normal pupils, and normal fundi. X-ray dorsal spine revealed scoliosis of thoracolumbar region. Magnetic resonance imaging (MRI) of the brain showed split sign of the pons and butterfly appearance of the medulla, which are the characteristic imaging features of this condition [Figure 2]. Hence, a diagnosis of HGPPS was made. Genetic analysis could not be performed due to logistic reasons.

Figure 2.

Magnetic resonance image depicting (a) T1 mid-sagittal cut showing “tenting of fourth ventricle” (b) T2/FLAIR axial cut at the level of pons shows “split pons sign” (c) T2/FLAIR axial cut at the level of medulla showing classical “Butterfly medulla”

HGPPS occurs due to ROBO3 gene mutation in chromosome 11q, which encodes a protein responsible for neuronal migration and axonal guidance.[1,2,3] Mutations of the ROBO3 gene cause disruption in crossing of embryonic brainstem neuronal pathways, leading to midline crossing defects specifically in the hindbrain, and affect major axon pathways, such as the corticospinal, dorsal column–medial lemniscus tracts, and medial longitudinal fasciculus.[4,5]

Horizontal gaze palsy occurs due to aberrant supranuclear input onto the abducens motor neurons from the pontine reticular formation and inability of the developing axons in the medial longitudinal fasciculus to cross the midline.[6] The reason for progressive scoliosis is not completely understood, although many theories have been proposed. One theory puts forward the poor development of extrapyramidal projections in the reticular formation as the probable cause. Involvement of the central tegmental tract along with primary dysfunction in the musculoskeletal system due to gene. Agenesis of afferent fibers within the inferior cerebellar peduncles and the pontocerebellar tracts has been quoted as another reason. Some others found no clear correlation between ROBO3 mutations and progressive scoliosis.[7,8]

MRI of the brain reveals a characteristic brainstem configuration with anterior and posterior midline clefts.[9] The pons is flattened and the facial colliculi do not protrude into the fourth ventricle, producing “split pons sign” and tenting of the fourth ventricle. The anterior cleft with the flattened medulla makes the medulla appear “Butterfly shaped”.[10] Our child had the characteristic MRI findings of split pons sign and butterfly medulla.

To conclude, any child presenting with horizontal gaze palsy should be looked for scoliosis. Neuroimaging will clinch the diagnosis. As it is an uncommon neurologic entity, understanding and documenting individual cases like this are crucial for advancing our knowledge, refining diagnostic approaches, and enhancing patient care.

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