Abstract
The enhanced S-cone syndrome (ESCS), a rare retinal degenerative disease often associated with NR2E3 mutation, is due to increased numbers of S-cones at the expense of other photoreceptors or miswiring distal to the photoreceptors. Paediatric ESCS and its differing clinical features (as opposed to adult ESCS) is the subject of this report.
BACKGROUND
The enhanced S-cone syndrome (ESCS), a rare retinal degenerative disease often associated with NR2E3 mutation,1–4 is due to increased numbers of S-cones at the expense of other photoreceptors or miswiring distal to the photoreceptors.5 Adults complain of hemeralopia, and are diagnosed from their unique retinal and electroretinogram (ERG) findings1–4: characteristic deep clumped pigmentary deposition around the vascular arcades,1–4 varying degrees of retinoschisis,1–4 a similar, simplified and delayed ERG waveform response to flashes under photopic and scotopic conditions2,3; and a delayed 30 Hz flicker ERG amplitude lower than that of the photopic a-wave.2,3 Paediatric enhanced S-cone syndrome (ESCS) has not been well described. Its differing clinical features are the subject of this report.
CASE PRESENTATION
Case 1 (3-year-old girl)
The patient’s mother had a history of poor night vision for many years. The patient had central/steady/maintained vision in either eye, 18-prism diopters esotropia at distance and near, and a cycloplegic refraction of +5.75−1.50×180 OD (right eye), +6.00−1.50×180 OS (left eye). Both eyes had an unhealthy retinal pigment epithelium (RPE) appearance with subfoveal lesions OU (fig 1A). Wearing her full cycloplegic refraction, the patient had no esotropia. Examination of her mother (fig 1B) showed no strabismus, uncorrected visual acuity of 20/60 OD and 20/200 OS, deep clumped pigmentation outside the vascular arcades OU, foveal schisis OS, and no significant cycloplegic refraction. ERGs were diagnostic for ESCS in mother and daughter (fig 2A, B). Mother and daughter were homozygous for a previously reported NR2E3 splice mutation (IVS1-2A→C).1 The father (the mother’s cousin) was confirmed as a carrier.
Figure 1.
(A) Case 1: in both eyes, the retinal pigment epithelium (RPE) had an unhealthy appearance, with scattered subretinal deposits most prominent in the fovea. No pigmentary deposits were seen. (B) Mother of case 1: the appearance was classic for enhanced S-cone syndrome, with deep clumped retinal pigmentary deposits and RPE atrophy outside the vascular arcades of both eyes. Foveal schisis was seen in the left eye (not shown). (C) Case 2: a prominent subretinal lesion was seen in a similar location in the posterior pole of both eyes (arrow). In addition, scattered small subretinal deposits and spots of pigments were present (arrowheads). (D) Case 3: The RPE had an unhealthy appearance, with scattered small subretinal deposits and subretinal spots of pigment (arrowheads). One larger subretinal deposit was adjacent to the disc in the right eye (arrow).
Figure 2.
The electroretinograms (ERGs) of (A) case 1, (B) her mother, (C) case 2 and (D) case 3 were diagnostic for enhanced S-cone syndrome (ESCS)—a similar, simplified and delayed waveform response to flash under photopic and scotopic conditions; and a delayed 30 Hz flicker amplitude lower than that of the photopic a-wave. The left tracings of each column are for the left eye and right tracings for the right eye. Stimulus intensities are described in logarithmic (log) units relative to the standard stimulus (1.5–3 Candela seconds/m2 at the surface of the Ganzfeld bowl). For each ERG in the first column (Rod Response), top tracings are for a minimal (0.25 log units) blue (430 nm) stimulus, middle tracings are for a standard (1.0 log unit) red (644 nm) stimulus, and bottom tracings are for a maximal (1.5 log units) white flash. Repeat recordings are seen in (A). In the second column (Cone Response), for the tracings in (A) and (C), the top tracings are for maximal flash with low background illumination (1 foot Lamberts), the middle tracings for standard flash with high background illumination (30 foot Lamberts), the second to last tracings are for maximal intensity flicker (30 Hz) with low background illumination, and the bottom tracings are for standard intensity flicker with low background illumination. Repeat recordings are seen for these tracings. In the second column for the tracings in (B) and (D), the top tracings are for maximal flash with low background illumination and the bottom tracings are for maximal intensity flicker with low background illumination; no repeats were done.
Case 2 (5-year-old boy)
The patient had a visual acuity of 20/80 OD and 20/40 OS, 20-prism diopters esotropia at distance, 25-prism diopters esotropia at near, and a cycloplegic refraction of +6.00−2.00×115 OD and +6.00−2.00×75 OS. There were multiple subretinal white deposits and an unhealthy appearance to the RPE (fig 1C). Wearing his full cycloplegic refraction, the patient had no esotropia at distance and 20/30 vision in either eye. An ERG was diagnostic for ESCS (fig 2C). Direct sequencing of NR2E3 was negative. Additional mutational analyses6,7 were not performed.
Case 3 (5-year-old boy)
The patient, not cooperative for visual acuity testing, had approximately 20-prism diopters esotropia at near. Cycloplegic refraction was +7.25 OU. Retinal examination was significant for subretinal white lesions (fig 1D). Wearing his full cycloplegic refraction, the patient had no esotropia at distance and 20/30 vision OU. An ERG was diagnostic for ESCS (fig 2D). NR2E3 sequencing showed homozygosity for a previously reported missense mutation (R311Q, CGG→CAG).
INVESTIGATIONS
Cycloplegic refractions, visual acuity testing, NR2E3 sequencing, ERGs and retinal examination.
DIFFERENTIAL DIAGNOSIS
Other retinal dystrophies.
TREATMENT
Genetic counselling, refractive correction.
DISCUSSION
Night blindness, refractive accommodative esotropia and subretinal lesions are presenting features of ESCS in young children.
The unique retinal phenotype that typically leads to the diagnosis of ESCS in adults was not observed in the children of this case series. The fact that the affected mother of case 1 exhibited the classic pattern of clumped pigmentation unique to ESCS led us to suspect the diagnosis in her 3-year-old daughter and raised our awareness for subsequent similar paediatric patients (cases 2 and 3). Murine models suggest that typical adult retinal phenotype develops over time.8 In one previously reported case, the characteristic retinal clumped pigmentation pattern developed between 9 and 11 years of age.4 The authors of that report also believed that significant hyperopia is a recurring feature of ESCS that may be missed without a cycloplegic refraction. Our case series suggests that night blindness, refractive accommodative oesotropia and subretinal lesions are presenting features of ESCS in young children.
LEARNING POINTS
Enhanced S-cone syndrome (ESCS), a retinal degenerative disease often associated with NR2E3 mutation, is due to increased numbers of S-cones at the expense of other photoreceptors or miswiring distal to the photoreceptors.
The unique retinal phenotype that typically leads to the diagnosis of ESCS in adults was not observed in these children.
Murine models suggest that typical adult retinal phenotype develops over time.
The diagnosis should be suspected in children presenting with refractive accommodative esotropia and retinal dystrophy.
Acknowledgments
This article has been adapted with permission from A O Khan, M Aldahmesh, B Meyer. The enhanced S-cone syndrome in children. Br J Ophthalmol 2007; 91: 394–6.
Footnotes
Competing interests: none.
REFERENCES
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