Phenotypic Variation in Enhanced S-cone Syndrome

Abstract

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.

NR2E3mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)

“…The p.F70F polymorphism was found in three RP patients and two controls of Swiss origin, and two controls of Algerian origin. In one Algerian control, p.F70F was present together with the previously reported p.G288G polymorphism [Audo et al, 2008]. The other novel polymorphism, p.G335G, was detected in a control of Swiss origin.…”

“…These two patients had no cystoid maculopathy or macular schisis, whereas a 20-yearold patient suffered from cystoid maculopathy, subretinal hemorrhage, and subfoveal neovascularization [Nakamura et al, 2002]. Macular schisis was found to be often associated with poor visual acuity, providing a clinical basis for the high variability in visual acuity with no correlation with age observed in patients [Audo et al, 2008]. Notably, a beneficial effect of the p.R311Q mutation was uncovered in presence of the adRP-linked p.G56R mutation, resulting in a more ESCS-like clinical phenotype in the compound heterozygous patients [Escher et al, 2009].…”

“…The loss of retinal lamination and the rosette formation in the ONL can be monitored during disease progression by spectral domain optical coherence tomography [Wang et al, in press]. Full-field electroretinogram (ERG) testing reveals the following characteristic findings: (1) no rod responses are recorded; (2) the waveforms of the scotopic maximal response are similar to those of the transient photopic response, except for reduced amplitudes in the a-and b-waves; (3) the amplitude of the a-wave in the transient photopic cone ERG is larger than the amplitude of the photopic 30-Hz flicker cone ERG; (4) the b-wave in the transient photopic cone ERG is large and prolonged, in contrast to a peaking b-wave in healthy subjects; (5) S-cone-specific ERG testing, using a blue stimulus (445 nm) on an orange background (620 nm) detects a remarkably high amplitude, i.e., 60 to 70 mV; and (6) L-and M-cone function is significantly reduced [Audo et al, 2008;Jacobson et al, 1990;Marmor, 2006;Marmor et al, 1990;Wang et al, in press]. …”

“…Histological analysis of a postmortem retina from a 77-year-old ESCS patient later confirmed an absence of rods and an increase by approximately two-fold of the number of cones, 92% of which were S-cones [Milam et al, 2002]. Additional clinical findings with an important variability and onset between patients, even inside a same family, including: cystoid maculopathy; retinal degeneration in the region of the vascular arcades, ranging from yellow flecks to clumped or nummular pigment deposition; relative ring scotomas; macular retinoschisis; disorganized retinal lamination; rosette formation in the outer nuclear layer; subfoveal neovascularization; and reduced visual acuity; posterior subcapsular cataracts [Audo et al, 2008;Cideciyan et al, 2003;Greenstein et al, 1996;Jacobson et al, 1990Jacobson et al, , 2004Jurklies et al, 2001;Marmor et al, 1990;Nakamura et al, 2004;Pachydaki et al, 2009;Vaclavik et al, 2008;Yamamoto et al, 1999]. The Goldmann-Favre syndrome (GFS; MIM] 268100) shared several clinical features with ESCS.…”

“…The present mutation update includes the many new NR2E3 mutations that have been reported in recent years, as well as new polymorphisms and unclassified sequence variants [Audo et al, 2008;Bandah et al, 2009;Bernal et al, 2008;Coppieters et al, 2007;Lam et al, 2007;Pachydaki et al, 2009]. Functional studies of mutant alleles, homology modeling of NR2E3, animal models of NR2E3 diseases, and clinical remarks are also presented.…”