Compound Heterozygous ROBO3 Mutation in Two Siblings Presenting with Horizontal Gaze Palsy without Scoliosis:...

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive disorder.
• It is characterized by congenital horizontal eye movement absence and progressive scoliosis.
• Mutations in the ROBO3 gene disrupt crucial nerve tract crossing in the medulla.

Purpose of the Study:

• To present two siblings diagnosed with HGPPS.
• To highlight the clinical and genetic findings in these cases.
• To emphasize the importance of evaluating eye movements and brainstem abnormalities in neurodevelopmental disorders.

Main Methods:

• Clinical evaluation of two affected siblings.
• Cranial MRI and diffusion tensor imaging (DTI) for brainstem abnormalities.
• ROBO3 gene sequencing to identify causative mutations.

Main Results:

• Both siblings presented with bilateral horizontal gaze palsy and varying degrees of psychomotor retardation.
• MRI and DTI revealed brainstem abnormalities, including absent decussation of corticospinal tracts.
• Compound heterozygous variations in the ROBO3 gene (IVS4-1G>A and c.328_329delinsCCC) were identified and segregated in the parents.

Conclusions:

• The findings confirm ROBO3 gene mutations as the cause of HGPPS in these siblings.
• Early assessment of eye movements and brainstem imaging is crucial for diagnosing HGPPS.
• This study underscores the link between ROBO3 mutations, HGPPS, and neurodevelopmental outcomes.