Clinical characteristics and radiological features of tubulinopathy: A single-center retrospective study in Japan

Tubulin plays an important role in cell morphogenesis and chromosomal segregation. Tubulinopathies are caused by pathogenic TUBA1A, TUBB2A, TUBB2B, TUBB3, TUBB4A, TUBB, and TUBG1 variants. Although radiological features and genotype-phenotype correlations of tubulinopathy have been described, clinical severity by genotype has not been described in detail. Herein, we discuss the correlations between the clinical and radiological features of head MRI of patients with tubulinopathy and its clinical severity by genotype.

We retrospectively reviewed medical records of patients diagnosed as having tubulinopathy at our hospital between January 2000 and May 2022.

Twelve (5 male, 7 female) patients were diagnosed with tubulinopathy: four with the TUBA1A variant, one with the TUBB2B variant, three with the TUBB3 variant, one with the TUBB variant, and three with the TUBB4A variant. All patients exhibited psychomotor delay; patients with perisylvian polymicrogyria-like cortical dysplasia had milder symptoms than those with generalized cortical dysplasia. Eight patients with epilepsy had good response to anti-seizure medications. Head MRI of all patients with TUBA1A, TUBB2B, TUBB3, and TUBB variants revealed basal ganglia dysplasia. All patients with the TUBB4A variant had cerebral white matter atrophy and delayed myelination, which were not found in patients with other variants.

The severity of psychomotor delay in patients with tubulinopathy may be related to the degree and extent of cortical dysplasia. Asymmetric basal ganglia dysplasia is a specific MRI finding of tubulinopathy. The clinical features and MRI findings associated with the TUBB4A variant differ from those of other tubulinopathies.