A Spectrum of Severity of a Unifying Retinal Phenotype in TUBB4B-Associated Inherited Retinal Degeneration

To increase our understanding of TUBB4B-associated autosomal dominant retinal degenerations through in-depth retinal phenotyping.

Two patients with pathogenic heterozygous variants in TUBB4B underwent a comprehensive ophthalmic exam, multimodal imaging with spectral domain optical coherence tomography (SD-OCT), ultra-widefield fundus imaging and short-wavelength (SW) and near infrared (NIR) fundus autofluorescence (FAF). Kinetic and chromatic dark- and light-adapted perimetry co-localized to the SD-OCT scans was performed in the older patient.

A 4 year old, high hyperope (+7D) boy sensorineural hearing loss (SNHL) since one year of age presented with surface elevation of the optic nerves concerning for papilledema. Visual acuities were 20/50 and 20/60 for the right and left eye, respectively. Evaluation revealed optic disc drusen, low-grade foveal hypoplasia and a retina-wide photoreceptor degeneration, most severe in the pericentral retinal sparing of the foveal center. A 43 year-old ∼6D myope woman with a 10-year-history of subtle visual field loss presented with normal visual acuities and generalized constriction of her kinetic fields. There as a retina-wide degeneration with a severe pericentral component encircled a normally laminated central island of normal rod- and cone photoreceptor function by chromatic perimetry. She reported no hearing loss. Genetic testing revealed heterozygous pathogenic variants in TUBB4B (c.1171C>T in the child, c.1168C>T variant in the adult patient).

We find in TUBB4B-associated retinal degeneration a predilection of disease to the pericentral retina with relative central sparing. The findings support a spectrum of severity within a recurring retinal phenotype that reconciles apparent phenotypic variability reported for this condition.