PURPOSE To characterize the ocular phenotype of DICER1 syndrome. DESIGN Prospective, single-center, case-control study. PARTICIPANTS One hundred three patients with an identified germline pathogenic DICER1 variant (DICER1 carriers) and 69 family control participants underwent clinical and ophthalmic examination at the National Institutes of Health between 2011 and 2016. METHODS All participants were evaluated with a comprehensive ophthalmic examination, including best-corrected visual acuity, slit-lamp biomicroscopy, and a dilated fundus examination. A subset of patients returned for a more detailed evaluation including spectral-domain OCT, color fundus photography, fundus autofluorescence imaging, visual field testing, full-field electroretinography, and genetic testing for inherited retinal degenerative diseases. MAIN OUTCOME MEASURES Visual acuity and examination findings. RESULTS Most DICER1 carriers (97%) maintained a visual acuity of 20/40 or better in both eyes. Twenty-three DICER1 carriers (22%) showed ocular abnormalities compared with 4 family controls (6%; P = 0.005). These abnormalities included retinal pigment abnormalities (n = 6 [5.8%]), increased cup-to-disc ratio (n = 5 [4.9%]), optic nerve abnormalities (n = 2 [1.9%]), epiretinal membrane (n = 2 [1.9%]), and drusen (n = 2 [1.9%]). Overall, we observed a significant difference (P = 0.03) in the rate of retinal abnormalities in DICER1 carriers (n = 11 [11%]) versus controls (n = 1 [1.5%]). One patient demonstrated an unexpected diagnosis of retinitis pigmentosa with a novel variant of unknown significance in PRPF31, and 1 showed optic nerve elevation in the setting of increased intracranial pressure (ICP) of unclear cause. Three patients (3%) demonstrated DICER1-related ciliary body medulloepithelioma (CBME), 2 of which were identified during routine examination, a higher rate than that reported previously. CONCLUSIONS Ophthalmologists should be aware of the ophthalmic manifestations of DICER1 syndrome, and individuals and families should be counseled on the potential signs and symptoms. We recommend that children with a germline pathogenic variant in DICER1, especially those younger than 10 years, undergo annual dilated ophthalmic examination, looking for evidence of CBME, signs of increased ICP, and perhaps changes in the retinal pigment epithelium.

中文翻译：

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DICER1综合征：在基于家庭的队列研究中眼表型的表征。

目的表征DICER1综合征的眼表型。设计前瞻性，单中心，病例对照研究。参与者2011年至2016年间，103名患有种系病原性DICER1变异体（DICER1携带者）的患者和69名家庭控制参与者在美国国立卫生研究院接受了临床和眼科检查。方法所有参与者均接受了全面的眼科检查评估，包括最佳眼科检查。矫正视力，裂隙灯生物显微镜检查和扩大的眼底检查。一部分患者返回进行更详细的评估，包括光谱域OCT，彩色眼底照相，眼底自体荧光成像，视野测试，全视野视网膜电图和遗传性视网膜退行性疾病的基因检测。主要观察指标视敏度和检查结果。结果大多数DICER1携带者（97％）的两只眼睛的视力都保持在20/40或更高。与4个家庭对照组（6％； P = 0.005）相比，二十三种DICER1携带者（22％）表现出眼部异常。这些异常包括视网膜色素异常（n = 6 [5.8％]），杯盘比增加（n = 5 [4.9％]），视神经异常（n = 2 [1.9％]），视网膜前膜（n = 2 [1.9％]）和玻璃疣（n = 2 [1.9％]）。总体而言，我们观察到DICER1携带者（n = 11 [11％]）与对照组（n = 1 [1.5％]）的视网膜异常率有显着差异（P = 0.03）。一名患者表现出意外的色素性视网膜炎诊断，其在PRPF31中具有未知意义的新型变体，1显示在不清楚原因的颅内压升高（ICP）的情况下出现视神经抬高。3例患者（3％）表现出与DICER1相关的睫状体上皮上皮瘤（CBME），其中2例是在常规检查中发现的，其发生率高于先前报道的水平。结论眼科医生应了解DICER1综合征的眼科表现，并应就可能的体征和症状向个人和家庭提供咨询。我们建议对DICER1具有种系致病变异的儿童，尤其是10岁以下的儿童，每年进行一次眼科散瞳检查，寻找CBME的证据，ICP升高的迹象，以及视网膜色素上皮细胞的变化。3例患者（3％）表现出与DICER1相关的睫状体上皮上皮瘤（CBME），其中2例是在常规检查中发现的，其发生率高于先前报道的水平。结论眼科医生应了解DICER1综合征的眼科表现，并应就可能的体征和症状向个人和家庭提供咨询。我们建议对DICER1具有种系致病变异的儿童，尤其是10岁以下的儿童，每年进行一次眼科散瞳检查，寻找CBME的证据，ICP升高的迹象，以及视网膜色素上皮细胞的变化。3例患者（3％）表现出DICER1相关的睫状体上皮细胞瘤（CBME），其中2例是在常规检查中发现的，其发生率高于先前报道的水平。结论眼科医生应了解DICER1综合征的眼科表现，并应就可能的体征和症状向个人和家庭提供咨询。我们建议对DICER1具有种系致病变异的儿童，尤其是10岁以下的儿童，每年进行一次眼科散瞳检查，寻找CBME的证据，ICP升高的迹象，以及视网膜色素上皮细胞的变化。并应就潜在的体征和症状向个人和家庭提供咨询。我们建议对DICER1具有种系致病变异的儿童，尤其是10岁以下的儿童，每年进行一次眼科散瞳检查，寻找CBME的证据，ICP升高的迹象，以及视网膜色素上皮细胞的变化。并应就潜在的体征和症状向个人和家庭提供咨询。我们建议对DICER1具有种系致病变异的儿童，尤其是10岁以下的儿童，每年进行一次眼科散瞳检查，寻找CBME的证据，ICP升高的迹象，以及视网膜色素上皮细胞的变化。