Intrafamilial variability of phenotype in CACNA2D4-associated retinal dysfunction: more or less

Introduction Retinal dysfunction associated with CACNA2D4 gene defects is a rare disorder of photoreceptor to bipolar cell signaling. We report two affected siblings presenting a surprising disparity of retinal involvement. Materials and methods Patients underwent complete ocular examination, multimodal fundus imaging, and full-field electroretinography (ffERG). Genetic testing was performed by a targeted Next Generation Sequencing panel. Results Two siblings presented a reduced visual acuity and light sensitivity. ffERG was specific for CACNA2D4 -related retinal dysfunction, but amplitudes of responses were different in the two patients. Additionally, an x-wave to a dim red flash was well preserved, and there was a reduced b/a ratio to a high intensity (30cd/m2) dark-adapted stimulus. Both patients were homozygous for the variant c.2406C > A, p.(Tyr802*) in CACNA2D4. During 17 years of follow-up, vision remained stable in patient 1, with no evidence of retinal degeneration. Conclusion Intrafamily clinical and electrophysiological expression of CACNA2D4- associated retinal dysfunction can be variable.