Phenotypic variation in enhanced S-cone syndrome.

PURPOSE: To characterize the clinical, psychophysical, and electrophysiological phenotype of 19 patients with enhanced S-cone syndrome (ESCS) and relate the phenotype to the underlying genetic mutation.
METHODS: Patients underwent ophthalmic examination and functional testing including pattern ERG, full-field ERG, and long-duration and short-wavelength stimulation. Further tests were performed in some patients, including color contrast sensitivity (CCS), multifocal ERG, fundus autofluorescence imaging (FAI), optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). Mutational screening of NR2E3 was undertaken in 13 patients.
RESULTS: The fundus appearance was variable, from normal to typical nummular pigment clumping at the level of the retinal pigment epithelium in older patients. Nine patients had foveal schisis, and one had peripheral schisis. Pattern ERG was abnormal in all patients. In all patients, ISCEV Standard photopic and scotopic responses had a similar waveform, the rod-specific-ERG was undetectable and the 30-Hz flicker ERG was markedly delayed with an amplitude lower than the photopic a-wave. Most ERG responses arose from short-wavelength-sensitive mechanisms, and a majority of patients showed possible OFF-related activity. Multifocal ERG showed relative preservation of central function, but reduced responses with increased eccentricity. Mutations were identified in NR2E3 in 12 of 13 patients including four novel variants.
CONCLUSIONS: The phenotype in ESCS is variable, both in fundus appearance and in the severity of the electrophysiological abnormalities. The ERGs are dominated by short-wavelength-sensitive mechanisms. The presence, in most of the patients, of possible OFF-related ERG activity is a finding not usually associated with S-cones.