A Complex Cortical Malformation Caused by a Mutation in the Tubulin-Encoding TUBB3 Gene

Abstract

Tubulinopathy commonly refers to complex congenital and non-progressive brain malformations caused by mutations in the tubulin genes. Among tubulin-encoding genes, TUBB3 has rarely been reported as a cause of complex cortical malformations. Herein, we report a case of tubulinopathy in a 21-month-old boy who presented with delayed development. He could not walk on his own and was not able to speak more than five words. Physical examination revealed right esotropia and hypotonia of the lower extremities. MRI showed dysmorphic brainstem and dysmorphic and hypertrophic basal ganglia. The right thalamus was relatively smaller than the left one. The cerebellum showed disorganization of the cerebellar folia. DNA sequencing revealed a missense mutation of the TUBB3 gene.

Loss of symmetric cell division of apical neural progenitors drivesDENND5A-related developmental and epileptic encephalopathy

“…Variants in tubulin genes also result in overlapping phenotypes 48 , but our cases lack the classic dysgyria pattern and instead are typically observed in the context of occipital pachygyria and differ in that our cases are associated with calcifications. Moreover, it seems that our cases have more severe basal ganglia abnormalities when compared with the typical imaging presentations associated with TUBA1A , TUBB2A , TUBB2B , TUBB3 , and TUBG1 49–51 . Variants in LIS1 , encoding a protein involved in neuronal migration, results most frequently in a posterior gradient of lissencephaly, without calcifications, and variable degrees of corpus callosum size including thin, normal, and thicker than normal tracts 52,53 .…”