A detailed phenotypic study of "cone dystrophy with supernormal rod ERG".
OBJECTIVE
To characterise the detailed phenotype of "cone dystrophy with supernormal rod ERG" in a case series of 10 patients.


METHODS
10 affected patients were examined clinically and underwent colour fundus photography, with nine undergoing detailed electrophysiological testing. Five patients were assessed further with fundus autofluorescence (AF) imaging, automated photopic and dark adapted perimetry, and dark adaptometry. Detailed colour vision assessment was performed in six subjects. Blood samples were taken from four patients for DNA extraction and mutation screening of NR2E3 was undertaken.


RESULTS
The onset of symptoms was in the first and second decades of life. Subjects presented with reduced central vision and marked photophobia. All individuals were myopic and colour vision testing revealed severely reduced colour discrimination predominantly along the red-green axes; tritan colour vision was relatively well preserved. Nyctalopia is a later feature of the disorder. Funduscopy and AF imaging revealed a range of macular appearances. There was electrophysiological evidence of marked macular dysfunction, reduced and delayed cone responses, and supernormal and delayed rod responses. Photopic and dark adapted perimetry revealed central scotomata with widespread peripheral sensitivity loss. No disease causing sequence variants in NR2E3 were identified.


CONCLUSIONS
The largest case series to date has been described of the clinical, psychophysical and electrophysiological characteristics of this unusual cone dystrophy with supernormal rod responses. Electrophysiological data were consistent with a post-phototransduction, but pre-inner nuclear layer, site of dysfunction. While the definitive diagnosis can only be made with electrophysiological testing, several characteristics that may increase suspicion of this diagnosis are presented.
Michaelides
M
M
Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
Holder
G E
GE
Webster
A R
AR
Hunt
D M
DM
Bird
A C
AC
Fitzke
F W
FW
Mollon
J D
JD
Moore
A T
AT
D000293:Adolescent; D000328:Adult; D003117:Color Vision Defects / Q000150:complications; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D009216:Myopia / Q000150:complications; D057093:Orphan Nuclear Receptors; D010641:Phenotype; D020795:Photophobia / Q000150:complications; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology*; D012174:Retinitis Pigmentosa / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D014157:Transcription Factors / Q000235:genetics; D058609:Visual Field Tests
C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors
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