为了描述详细的表型,长期临床过程,临床变异性,增强S-锥综合征(ESCS)患者的基因型。
回顾性病例系列。
56例ESCS患者。
临床病史,考试,成像,和56例患者的电生理检查结果(年龄范围,1-75岁)诊断为ESCS进行了回顾。通过NR2E3基因中致病变异的分子确认(n=38)或通过诊断性全场视网膜电图发现(n=18)来建立诊断。
视觉症状发作的年龄,最佳矫正视力(BCVA),定量与年龄相关的电生理衰退,和成像发现。
出现视觉症状的平均年龄为4.0岁,演示时的平均年龄为20.5岁,平均随访间隔为6.1年。对6名患者进行了一次评估。在38例患者中发现NR2E3的致病变异。视力较好的眼睛的平均BCVA在基线时为最小分辨率角(logMAR)的0.32对数,在随访时为0.39logMAR。在大多数人眼中(76%[76/100]),BCVA保持稳定,随访期间平均BCVA变化为0.07logMAR。错视是最常见的初始症状,92.9%的患者报告(52/56)。临床检查结果差异很大,包括中央窝裂开(41.1%[26/56]),黄白色圆点(57.1%[32/56]),色素沉着(85.7%[48/56]),鱼雷样病变(10.7%[6/56]),和环状视网膜下纤维化(7.1%[4/56])。自发荧光的黄斑和周边模式被分类为(1)最小变化,(2)低自发荧光(轻度弥漫性,中度斑点,中度弥漫性,或高级),或(3)强自发荧光斑点。一名患者表现出无法检测到的视网膜电描记术结果;所有其他患者的主要视网膜电描记术成分的定量显示出振幅和峰值时间变异性,但具有病理特征视网膜电描记术特征。视网膜电图的主要成分显示出与年龄有关的恶化超过6.7年的证据,与未受影响的对照参与者的比率没有区别。鉴定出NR2E3中的18个序列变体,包括4个小说错义变化。
增强的S-锥综合征具有高度可变的表型,随着时间的推移具有相对的临床和成像稳定性。大多数视网膜电图检查结果具有病理特征,但是定量评估揭示了变异性和与年龄相关的正常平均下降率,与大部分非进行性周围视网膜功能障碍一致。
To describe the detailed phenotype, long-term clinical course, clinical variability, and genotype of patients with enhanced S-cone syndrome (ESCS).
Retrospective
case series.
Fifty-six patients with ESCS.
Clinical history, examination, imaging, and electrophysiologic findings of 56 patients (age range, 1-75 years) diagnosed with ESCS were reviewed. Diagnosis was established by molecular confirmation of disease-causing variants in the NR2E3 gene (n = 38) or by diagnostic full-field electroretinography findings (n = 18).
Age at onset of visual symptoms, best-corrected visual acuity (BCVA), quantitative age-related electrophysiologic decline, and imaging findings.
Mean age at onset of visual symptoms was 4.0 years, and median age at presentation was 20.5 years, with mean follow-up interval being 6.1 years. Six patients were assessed once. Disease-causing variants in NR2E3 were identified in 38 patients. Mean BCVA of the better-seeing eye was 0.32 logarithm of the minimum angle of resolution (logMAR) at baseline and 0.39 logMAR at follow-up. In most eyes (76% [76/100]), BCVA remained stable, with a mean BCVA change of 0.07 logMAR during follow-up. Nyctalopia was the most common initial symptom, reported in 92.9% of patients (52/56). Clinical findings were highly variable and included foveomacular schisis (41.1% [26/56]), yellow-white dots (57.1% [32/56]), nummular pigmentation (85.7% [48/56]), torpedo-like lesions (10.7% [6/56]), and circumferential subretinal fibrosis (7.1% [4/56]). Macular and peripheral patterns of autofluorescence were classified as (1) minimal change, (2) hypoautofluorescent (mild diffuse, moderate speckled, moderate diffuse, or advanced), or (3) hyperautofluorescent flecks. One patient showed undetectable electroretinography findings; quantification of main electroretinography components in all other patients revealed amplitude and peak time variability but with pathognomonic electroretinography features. The main electroretinography components showed evidence of age-related worsening over 6.7 decades, at a rate indistinguishable from that seen in unaffected control participants. Eighteen sequence variants in NR2E3 were identified, including 4 novel missense changes.
Enhanced S-cone syndrome has a highly variable phenotype with relative clinical and imaging stability over time. Most electroretinography findings have pathognomonic features, but quantitative assessment reveals variability and a normal mean rate of age-related decline, consistent with largely nonprogressive peripheral retinal dysfunction.