A 10-month-old boy presented with motor developmental delay, torticollis, bilateral abduction restriction (incomplete horizontal gaze palsy), and left lower motor neuron facial palsy. His brain MRI demonstrated brainstem malformations, including absent facial colliculi (Figure, A), clefting of the medulla and pons (Figure, B), butterfly configuration of the medulla (Figure, C), and concave dorsal pontine border (Figure, D). Genetic testing revealed a homozygous missense mutation (c.437G > C [p.Arg146Pro]) in exon 2 of the ROBO3 gene. Horizontal gaze palsy with progressive scoliosis (HGPPS1) results from axonal guidance signalling defects caused by ROBO3 mutations.1 The main symptoms include congenital horizontal gaze palsy, horizontal pendular nystagmus, and progressive scoliosis after 2 years of age. The radiologic differential for this hindbrain malformation is horizontal gaze palsy with progressive scoliosis-2, caused by mutation in the DCC gene.2 Children with HGPPS2 also demonstrate intellectual impairment and agenesis of the corpus callosum.2
Figure. Imaging Findings of ROBO3 Mutation.
High-resolution heavily weighted T2 (CISS) axial images demonstrate (A) absent facial colliculi (arrowhead), (B) dorsal pontine cleft generating the split pons sign (arrowhead), and (C) butterfly configuration of medulla. T2 sagittal image demonstrates (D) pontine hypoplasia (dashed arrow), concave dorsal pontine border (arrowhead), and normal corpus callosum.
Footnotes
Teaching slides links.lww.com/WNL/C576
Author Contributions
G. Chanda: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. N. Reddy: drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data. R. Konanki: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. E. Boltshauser: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. L. Lingappa: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data.
Study Funding
The authors report no targeted funding.
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
References
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