A Novel Case of CACNA1F Mutation Causing Congenital Nystagmus

Objective: To describe a case of congenital (infantile) nystagmus with a pathogenic mutation in CACNA1F that extends the phenotype of CACNA1F conditions. Background: CACNA1F constitutes the major molecular correlate of the retinal L-type calcium current. Its intrinsic biophysical properties enable it to provide a sustained calcium current over the voltage range required for tonic glutamate release at the photoreceptor synapse. The CACNA1F gene is located on Xp11.23. Genetic mutations have been reported to be associated with X-Linked ocular conditions such as Aland Island eye disease, Cone-rod dystrophy (type 3) and Congenital stationary night blindness (type 2A). Design/Methods: We report the case of a 28 year old man with congenital (infantile) nystagmus without other symptoms and in particular no significant degradation of his vision (day or night-time) over time. Ocular exam showed myopia but nil else of note. His maternal uncle has a similar phenotype. Results: MRI brain and orbits showed small optic nerves, in particular on axial T1 images. Genetic testing revealed the patient to be hemizygous for the variant c.5479C>T p.(Arg1827Ter) in the CACNA1F gene. The available evidence in published literature suggests that this is a pathogenic variant. Conclusions: This patient’s presentation does not fit entirely with any of the three ocular conditions associated with CACNA1F mutations reported in the literature to date. This case therefore extends the phenotypic spectrum of CACNA1F conditions with a novel genetic variant. Disclosure: Dr. Doyle has nothing to disclose. Dr. Healy has nothing to disclose.