Clinical Characteristics

The clinical spectrum associated with pathogenic variants in TUBB2A is heterogeneous.
Affected individuals usually present in the first year of life with hypotonia, seizures or developmental delay. Affected individuals have mild to severe intellectual disability. Motor development can be mildly affected while a subset of patients never achieves independent ambulation. Speech development is often lacking. Epilepsy is common and has been reported in 85% of patients, but the age of onset (neonatal period to 5 years) and type of seizures are variable. A subset of patients presents with mild and non-specific facial dysmorphisms, poor visual contact and microcephaly.

Brain imaging can be normal to severely abnormal. The cerebral cortex displays tubulinopathy-related dysgyria, that can resemble diffuse polymicrogyria in severely affected individuals. Associated brain malformations including hypoplasia or dysplasia of the corpus callosum, the basal ganglia and the cerebellum, occur less frequently than in other tubulinopathies. The brainstem is usually normal.

To date, progressive spastic paraplegia and cerebral atrophy has been reported in one patient.