Diagnostic Clinical Findings of a New Syndrome with Night Blindness, Maculopathy, and Enhanced S Cone Sensitivity

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

“…All patients affected with NR2E3-linked recessive retinal degenerations, i.e., ESCS, GFS and CRPD, consistently present with night blindness from early in life Marmor, 2006;Marmor et al, 1990]. Fundus examination in adult patients typically reveals mid-peripheral nummular pigment clumping along the vascular arcades, and the subtle pigmentary changes with white dots observed in young patients may represent an early stage of the disease process [Khan et al, 2007;Sharon et al, 2003;Wang et al, in press].…”

“…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]. …”

“…All patients presented with night blindness from early in life and are characterized by unique fullfield and spectral electroretinographic (ERG) findings Marmor et al, 1990]. In response to blue and red stimuli, a hyperfunction of S-cones (''blue'' cones) was detected, with impaired M-and L-cone functions.…”

“…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.…”

Clinical features of the congenital vitreoretinopathies

“…The electroretinogram (ERG) shows absent rod-isolated responses under dark adaptation, while rod and cone dark-and light-adapted waveforms are similar with delayed and broadened responses. 19 Very rare cases present with vitreoretinal degeneration, and these are referred to as GoldmannFavre. Thus, ESCS may best be categorized as a retinal degeneration with macular and retinal degeneration, rather than a vitreoretinal degeneration.…”