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J Pediatr Genet
DOI: 10.1055/s-0041-1739387
Case-Based Review

Compound Heterozygous ROBO3 Mutation in Two Siblings Presenting with Horizontal Gaze Palsy without Scoliosis: Case-Based Review

Adnan Deniz 
1   Department of Pediatrics, Division of Child Neurology, Kocaeli Universitesi, Kocaeli, Turkey
,
Sinan Çomu
2   Department of Pediatrics, Division of Child Neurology, Anadolu Health Center, Kocaeli, Turkey
,
Mesut Güngör 
1   Department of Pediatrics, Division of Child Neurology, Kocaeli Universitesi, Kocaeli, Turkey
,
Yonca Anık 
3   Deparment of Radiology, Kocaeli University, Kocaeli, Turkey
,
Bülent Kara 
1   Department of Pediatrics, Division of Child Neurology, Kocaeli Universitesi, Kocaeli, Turkey
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Abstract

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessively inherited disorder characterized by a congenital absence of conjugated horizontal eye movements with progressive scoliosis developing in childhood and adolescence. HGPPS is caused by mutations of the ROBO3 gene that disrupts the midline crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. We present two siblings, 5-year-old and 2-year-old boys with HGPPS, from non-consanguineous parents. The older brother was brought for the evaluation of moderate psychomotor retardation. He had bilateral horizontal gaze palsy with preserved vertical gaze and convergence. Scoliosis was absent. Cranial MRI showed brainstem abnormalities, and diffusion tensor imaging showed absent decussation of cortico-spinal tracts in the medulla. Clinical diagnosis of HGPPS was confirmed by sequencing of ROBO3 gene, IVS4–1G > A (c.767–1G > A) and c.328_329delinsCCC (p.Asp110Profs*57) compound heterozygous variations were found, and segregated in parents. The younger boy was first reported at 16 months of age and had the same clinical and neuroradiological findings, unlike mild psychomotor retardation. ROBO3 gene analysis showed the same variants in his brother. Our cases show the importance of evaluating eye movements in children with neurodevelopmental abnormalities and looking for brainstem abnormalities in children with bilateral horizontal gaze palsy.

Keywords

ROBO3 - horizontal gaze palsy - progressive scoliosis - brainstem abnormalities - midline crossing


Publication History

Received: 06 April 2021

Accepted: 29 September 2021

Article published online:
09 November 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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