TUBB3 GENE MUTATION ARG262HIS BEYOND CRANIAL DYSINNERVATION: EVIDENCE OF MALFORMATION OF CORTICAL DEVELOPMENT

Abstract

Background: Pathogenic variants in TUBB3 are associated with a spectrum of neurodevelopmental disorders, including congenital cranial dysinnervation disorders and tubulinopathies affecting neuronal migration.

Methods and Result: We report a preterm female infant with a heterozygous pathogenic TUBB3 variant (c.785G>A; p. Arg262His) presenting in the neonatal period with severe respiratory distress, feeding difficulty, cranial nerve dysfunction, and multiple congenital contractures. Brain MRI demonstrated malformations of cortical development, including a simplified gyral pattern, cortical thickening, basal ganglia dysplasia with fusion of the caudate and putamen, thalamic asymmetry, distortion of the interhemispheric fissure, inferior vermian hypoplasia, and thinning of the corpus callosum. Ophthalmologic findings included absent blinking and early corneal involvement.

Conclusion: This case expands the phenotypic spectrum of the TUBB3 p.Arg262His variant by demonstrating significant malformations of cortical development and highlighting severe early cranial nerve dysfunction with vision-threatening ocular surface complications.