Pontine malformation, undecussated pyramidal tracts, and regional polymicrogyria: a new syndrome

Abstract

Background: Horizontal gaze palsy and progressive scoliosis is caused by mutations in the ROBO3 gene, which plays a role in axonal guidance during brain development. Horizontal gaze palsy and progressive scoliosis is characterized by the congenital absence of conjugate lateral eye movements with preserved vertical gaze and progressive scoliosis as well as dysgenesis of brainstem structures and ipsilateral projection of the pyramidal tract.

Patient: A 4-year, 11-month, girl presented with psychomotor retardation and autistic traits. Magnetic resonance imaging revealed hypoplasia and malformation of the ventral portion of the pons and medulla oblongata. Diffusion tensor imaging revealed the absence of decussation of the bilateral pyramidal tracts. These findings were similar to the typical findings for horizontal gaze palsy and progressive scoliosis. However, restriction of horizontal eye movement was minimal, and bilateral polymicrogyria were also noted in the occipitotemporal cortex in the present patient. These findings have not been previously reported in patients with horizontal gaze palsy and progressive scoliosis. No mutations in the ROBO3, SLIT1, SLIT2, NTN1, SEMA3 A, or SEMA3 F genes were identified.

Conclusion: This child may have a disorder caused by an unidentified factor, other than a mutation in the genes analyzed, involved in corticogenesis, axonal guidance, and brainstem morphogenesis.

Keywords: axonal guidance; brainstem hypoplasia; decussation of the pyramidal tract; horizontal gaze palsy; polymicrogyria; pontine malformation; progressive scoliosis.

Figure 1

Brainstem structures visualized on magnetic resonance imaging (MRI) of the patient at 2.5 years of age (A: T1-weighted sagittal section; B to F: constructive interference in steady-state sequences). A: The brainstem tegmentum appears hypoplastic at the level of the isthmus, and the protrusion of the ventral pons is attenuated. B: A molar tooth-like appearance is noted at the isthmus, composed by parallel orientation of superior cerebellar peduncles and an enlarged forth ventricle. B to E: A cleft (thick arrow) is seen at the midline along the entire length of the ventral pons. Small colliculi are noted on both sides of this cleft (long arrows in E). C: Entry of the trigeminal nerve roots (arrows) is dislocated to the most lateral end of the ventral pons. D: The abducens nerves (arrows) originate at the colliculli lateral to the midline cleft. E: The facial (arrows) and vestibulocochlear (arrowheads) nerves, which normally leave the brainstem in parallel and closely apposed to each other, originate separately.

Figure 2

Supratentorial structures on MRI (A, B, D and E: T2-weighted images; C: T1-weighted image). The cerebral cortex is thick in the posterior areas, including the bilateral temporal and occipital lobes (white arrows in B and C). The multi-convoluted cortical surface (C) and irregular gray-white matter boundary (B, C) are compatible with the findings in polymicrogyria. A myelinated layer is noted regionally within the thick cortex, which is suggestive of subcortical heterotopia (arrows in E). In D, hippocampal formation appears somewhat plump, but is not obviously dysplastic.

Figure 3

Diffusion tensor images of the bilateral pyramidal tracts. The tract from the right precentral gyrus is seen in blue (A), and that from the left precentral gyrus is seen in yellow (B). The levels of the central sulcus, the basal ganglia, the midbrain, the rostral and caudal pons, the rostral and caudal medulla oblongata, and the medullospinal transition are shown from top to bottom. Note that these pathways descend through the ipsilateral brainstem, and there is no evidence of decussation. Anomalous Sylvian fissures can be observed in the images at the level of central sulcus.