多族裔亚洲队列中成人起病CLN相关视网膜变性的炎症性伪装特征

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中文摘要

目的： 描述一个多族裔亚洲队列中非综合征型神经元蜡样脂褐质沉积症（NCL）相关视网膜变性的临床、影像学和遗传学特征，特别关注最初被纳入非肿瘤性葡萄膜炎伪装综合征鉴别诊断的病例。
方法： 本回顾性病例系列回顾了7例经基因确诊为CLN相关遗传性视网膜变性的无亲缘关系新加坡患者（华裔和印度裔）。分析了临床表现、炎症特征、纵向多模态影像、电生理和分子学发现。
结果： 症状起病年龄为18至54岁。就诊症状包括“视物模糊/飞蚊症（n=3）”、“夜盲（n=3）”和“昼盲（n=1）”。5例患者表现为活动性眼部炎症，如前房和玻璃体细胞及视网膜血管炎。值得注意的是，另外2例患者（携带CLN2和CLN3变异）未显示明显的前节或后节炎症；然而，其显著的结构和影像学表现与炎症性视网膜病变相似，促使将其纳入伪装综合征鉴别诊断。在所有7例患者中，系列光学相干断层扫描（OCT）显示持续的外层视网膜萎缩和椭圆体带丢失。5例患者中有1例接受了糖皮质激素和免疫抑制治疗，但反应有限，而其余4例对局部、眼周或口服糖皮质激素反应良好。在2.7至33.1年的随访期间，中位最佳矫正视力下降至logMAR 1.90。除1例CLN2相关病例出现成人起病感音神经性听力损失外，全身健康状况保持稳定，无神经系统症状。通过基因检测鉴定出CLN1、CLN2、CLN3、CLN5和CLN7的致病性变异。CLN相关疾病占该队列遗传性视网膜疾病家系的1.1%。
结论： 在我们的队列中，与CLN1、CLN5和CLN7变异相关的视网膜变性常表现为眼内炎症（范围从前葡萄膜炎到全葡萄膜炎）。然而，即使没有明显炎症体征的患者也经历了持续的视网膜功能下降，其表现与严重后葡萄膜炎中所见的结构损害高度相似。这些发现凸显了在评估非典型、对称性后葡萄膜炎或疑似伪装综合征时，早期基因检测为何至关重要。

英文摘要

PURPOSE: To describe the clinical, imaging, and genetic features of non-syndromic neuronal ceroid lipofuscinosis (NCL)-associated retinal degeneration in a multi-ethnic Asian cohort, with particular emphasis on cases that were initially considered in the differential diagnosis of non-neoplastic uveitis masquerade syndromes.
METHODS: This retrospective case series reviewed seven unrelated Singaporean patients (Chinese and Indian ancestry) with genetically confirmed CLN-associated inherited retinal degeneration. Clinical presentation, inflammatory features, longitudinal multimodal imaging, electrophysiology, and molecular findings were analyzed.
RESULTS: Symptom onset ranged from 18 to 54 years. Presenting symptoms included "blurred vision/floaters (n = 3)", "nyctalopia (n = 3)", and "hemeralopia (n = 1)". Five patients presented with active ocular inflammation, such as anterior chamber and vitreous cells and retinal vasculitis. Notably, the other two patients (harboring CLN2 and CLN3 variants) did not show overt anterior or posterior segment inflammation; however, their striking structural and imaging similarities to inflammatory retinopathies prompted their inclusion in the masquerade differential. Across all seven patients, serial optical coherence tomography (OCT) revealed relentless outer retinal atrophy and loss of the ellipsoid zone. One of the five patients received corticosteroid and immunosuppressive therapy but showed only a limited response, whereas the remaining four patients responded favourably to topical, periocular, or oral corticosteroids. During a follow-up of 2.7-33.1 years, median best-corrected visual acuity declined to logMAR 1.90. Systemic health remained stable without neurological symptoms, except for one CLN2-associated case developing adult-onset neurosensory hearing loss. Pathogenic variants in CLN1, CLN2, CLN3, CLN5, and CLN7 were identified through genetic testing. CLN-associated disease accounted for 1.1% of the inherited retinal disease families in the cohort.
CONCLUSIONS: Retinal degeneration associated with CLN1, CLN5, and CLN7 variants frequently presented with intraocular inflammation (ranging from anterior to panuveitis) in our cohort. Yet even patients without obvious inflammatory signs experienced a relentless retinal decline that closely mimicked the structural damage seen in severe posterior uveitis. These findings highlight why early genetic testing is so crucial when working up atypical, symmetrical posterior uveitis or suspected masquerade syndromes.