Expanding the adult spectrum of TUBB4A disease: a spasticity–tremor phenotype with network imaging correlates

TUBB4A mutations cause a spectrum of neurological disorders, but adult-onset hereditary spastic paraplegia is rarely described. We characterized a Turkish family with a novel TUBB4A nucleotide variant (c.1023 C > A, p.Phe341Leu) using clinical, genetic, and advanced neuroimaging (VBM, DTI) compared to 15 controls. The proband exhibited late-onset spasticity, tremor and mild frontal executive dysfunction. Routine MRI showed posterior-predominant white matter hyperintensities. VBM revealed subclinical gray matter atrophy in the basal ganglia, thalami, and cerebellum, while DTI demonstrated widespread microstructural damage across motor and associative tracts. Our findings expand the clinicoradiological spectrum of TUBB4A disorders, suggesting distributed structural abnormalities despite relatively mild clinical expression.