Expanded clinical spectrum of enhanced S-cone syndrome

Abstract

Importance: New funduscopic findings in patients with enhanced S-cone syndrome (ESCS) may help clinicians in diagnosing this rare autosomal recessive retinal dystrophy.

Objective: To expand the clinical spectrum of ESCS due to mutations in the NR2E3 gene.

Design: Retrospective, noncomparative case series of 31 patients examined between 1983 and 2012.

Setting: Academic and private ophthalmology practices specialized in retinal dystrophies.

Participants: A cohort of patients diagnosed with ESCS and harboring known NR2E3 mutations.

Intervention: Patients had ophthalmic examinations including visual function testing that led to the original diagnosis.

Main outcomes and measures: New fundus features captured with imaging modalities.

Results: New clinical observations in ESCS include (1) torpedo-like, deep atrophic lesions with a small hyperpigmented rim, variably sized and predominantly located along the arcades; (2) circumferential fibrotic scars in the posterior pole with a spared center and large fibrotic scars around the optic nerve head; and (3) yellow dots in areas of relatively normal-appearing retina.

Conclusions and relevance: Enhanced S-cone syndrome has more pleiotropy than previously appreciated. While the nummular type of pigmentation at the level of the retinal pigment epithelium and cystoid or schisis-like maculopathy with typical functional findings remain classic hallmarks of the disease, changes such as circumferential fibrosis of the macula or peripapillary area and "torpedo-like" lesions along the vascular arcades may also direct the clinical diagnosis and focus on screening the NR2E3 gene for a molecular diagnosis.

Figure 1. Color Composite of the Right and Left Eyes of Patient 1

Twenty–five-year-old woman homozygous for the R311Q mutation. Visual acuity is 20/200 OD and 20/25 OS. There are large circumferential fibrotic lesions in the posterior poles of both eyes (interrupted arrow). The fovea is present (continuous arrow). Along the superior arcades, torpedo-like lesions are noted (asterisk). Small yellow dots interspersed with nummular pigmentations are present in both eyes, mainly nasal inferior to the disc (arrowhead).

Figure 2. High-Resolution Optical Coherence Tomography Scans Horizontally Across Both Eyes of Patient 1

Twenty–five-year-old woman homozygous for the R311Q mutation. A, Right eye. B, Left eye. There is outer retinal tubulation (asterisk), subretinal fibrosis (arrowhead), retained inner segment of ellipsoid band subfoveally (arrow), and loss of retinal organization.

Figure 3. Composite of Fundus Autofluoresence Images of Both Eyes of Patient 1

Twenty–five-year-old woman homozygous for the R311Q mutation. A large hypoautofluorescent ring is present (asterisk) with a hyperautofluorescent center (arrow). In the periphery, different patterns of autofluorescence are present. The yellow dots seen on the color photographs appear hyperautofluorescent (arrowhead).

Figure 4. Varying Locations and Extents of Subretinal Fibrosis in Enhanced S-Cone Syndrome

A, The right eye of patient 2 (15-year-old boy homozygous for the IVS1-2A>C mutation) shows large fibrosis surrounding the nerve head and extending superiorly. B, The left eye of patient 2 at age 15 years with a circumferential scar around the nerve head. C, Unilateral fibrotic scarring of the posterior pole in patient 3 (17-year-old boy homozygous for the R311Q mutation). D, Patient 4 (46-year-old woman homozygous for the R311Q mutation) shows bilateral scarring in the posterior pole. The right eye shows scarring in a circumferential manner around the fovea. E, Patient 5 (40-year-old woman homozygous for the R311Q mutation) has fibrosis in the posterior poles of both eyes. The right eye shows fibrosis extending from the peripapillary area to the temporal retina following the inferior arcade and sparing the fovea. F, Patient 6 (6-year old boy homozygous for the R311Q mutation) has a central scar in the right eye. The left eye shows subtle subretinal fibrosis along the inferior arcade, sparing the fovea (not shown). G, The right eye of patient 7 (4-year-old girl homozygous for the p.C67-69Gdel mutation) shows subretinal fibrosis inferior to the optic disc. H, The left eye of patient 7 shows subretinal fibrosis superior to the optic disc.

Figure 5. Torpedo-like Lesions in Enhanced S-Cone Syndrome

A, Patient 8 (54-year-old man homozygous for the R311Q mutation) shows a large hyperpigmented lesion with multiple atrophic areas along the superior arcade in the right eye. B, Patient 9 (41-year-old man with the R311Q and IVS1-2A>C mutations) has multiple hyperpigmented spots. Some of these lesions show atrophic centers. C, A large and more typical oval torpedo-like lesion just inferior of the superior arcade of the right eye of patient 1 (25-year-old woman homozygous for the R311Q mutation). D, Multiple hyperpigmented round lesions variable in size, most of which have an atrophic center, in the right eye of patient 10 (55-year-old woman homozygous for the R311Q mutation). E, The left eye of patient 11 (35-year-old man with the R311Q and Q350R mutations) shows multiple oval torpedo-like lesions along the arcades. The 2 enlarged images are from photographs taken in 1999 (I) and 2010 (II) and show no obvious change in appearance. F, One larger oval torpedo-like lesion in an area of hyperpigmentation inferior to the disc and arcade in the left eye of patient 12 (72-year-old woman).

Figure 6. Yellow Dots in Enhanced S-Cone Syndrome

A, The right eye of patient 2 (15-year-old boy homozygous for the IVS1-2A>C mutation) shows multiple small subretinal yellow dots only present in an area of normal-appearing retina. The dots are located temporal to the fovea. There is fibrosis along the disc. B, The right eye of patient 4 (46-year-old woman homozygous for the R311Q mutation) shows different-sized yellow dots nasal to the optic nerve. The yellow dots are interspersed with hyperpigmented dots. There is fibrosis in the posterior pole. C, The left eye of patient 4 (46-year-old woman homozygous for the R311Q mutation) shows a large area of confluent-appearing white dots nasal and superior to the nerve head. The nummular type of pigmentation is also present.