Clinical and molecular characteristics of childhood-onset Stargardt disease.
Clinical and molecular characteristics of childhood-onset Stargardt disease.
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DOI：
10.1016/j.ophtha.2014.08.012
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发表时间：
2015-02
期刊：
影响因子：
13.7
通讯作者：
Moore, Anthony T.
中科院分区：
文献类型：
--
作者：
Fujinami, Kaoru;Zernant, Jana;Chana, Ravinder K.;Wright, Genevieve A.;Tsunoda, Kazushige;Ozawa, Yoko;Tsubota, Kazuo;Robson, Anthony G.;Holder, Graham E.;Allikmets, Rando;Michaelides, Michel;Moore, Anthony T.
描述儿童期发病的Stargardt病（STGD）患者的临床和分子特征。回顾性病例系列。2001年1月至2012年1月期间，在一家机构中，有42名儿童期被诊断出患有STGD的患者。进行详细的病史和全面的眼科检查，包括彩色眼底照相、自体荧光成像、光谱域光学相干断层扫描（SD-OCT）、模式和全视野视网膜电图。使用下一代基于测序的策略筛选ABCA 4的整个编码区和剪接位点。儿童期发病的STGD患者的分子遗传学研究结果进行了比较与成人发病的患者。临床、影像学、电生理学和分子遗传学发现。中位发病年龄和基线检查时的中位年龄分别为8.5岁（范围，3-16岁）和12.0岁（范围，7-16岁）。最小分辨角视力的中位基线对数为0.74。在基线时，39例有可用照片的患者中有26例（67%）有黄斑萎缩伴黄斑/周边软化; 11例（28%）有黄斑萎缩不伴软化; 1例（2.5%）有大量软化不伴黄斑萎缩; 1例（2.5%）眼底外观正常。12例患者（31%）在基线时未发现斑点。SD-OCT在所有21例具有可用图像的患者中检测到中央凹外视网膜破裂。电生理评估显示9例患者（36%）的视网膜功能障碍仅限于黄斑，1例受试者（4%）的黄斑和全身性锥体功能障碍，15例受试者（60%）的黄斑和全身性锥体和杆功能障碍。在38例患者（90%）中确定了至少1种致病ABCA 4变异，包括13种新变异;在34例患者（81%）中确定了≥2种变异。儿童期发病的STGD患者比成人期发病的STGD患者更常携带2种有害变异（18% vs 5%）。儿童期发作的STGD与严重的视力丧失、早期形态学改变和通常的全身性视网膜功能障碍相关，尽管在检查时通常具有不太严重的眼底异常。三分之一的孩子在介绍时没有慌乱。相对高比例的有害ABCA 4变体支持了这样的假设，即早发性疾病通常是由于ABCA 4中比成人发病疾病中发现的那些更严重的变体。
To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD). Retrospective case series. Forty-two patients who were diagnosed with STGD in childhood at a single institution between January 2001 and January 2012. A detailed history and a comprehensive ophthalmic examination were undertaken, including color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and pattern and full-field electroretinograms. The entire coding region and splice sites of ABCA4 were screened using a next-generation, sequencing-based strategy. The molecular genetic findings of childhood-onset STGD patients were compared with those of adult-onset patients. Clinical, imaging, electrophysiologic, and molecular genetic findings. The median ages of onset and the median age at baseline examination were 8.5 (range, 3–16) and 12.0 years (range, 7-16), respectively. The median baseline logarithm of the minimum angle of resolution visual acuity was 0.74. At baseline, 26 of 39 patients (67%) with available photographs had macular atrophy with macular/peripheral flecks; 11 (28%) had macular atrophy without flecks; 1 (2.5%) had numerous flecks without macular atrophy; and 1 (2.5%) had a normal fundus appearance. Flecks were not identified at baseline in 12 patients (31%). SD-OCT detected foveal outer retinal disruption in all 21 patients with available images. Electrophysiologic assessment demonstrated retinal dysfunction confined to the macula in 9 patients (36%), macular and generalized cone dysfunction in 1 subject (4%), and macular and generalized cone and rod dysfunction in 15 individuals (60%). At least 1 disease-causing ABCA4 variant was identified in 38 patients (90%), including 13 novel variants; ≥2 variants were identified in 34 patients (81%). Patients with childhood-onset STGD more frequently harbored 2 deleterious variants (18% vs 5%) compared with patients with adult-onset STGD. Childhood-onset STGD is associated with severe visual loss, early morphologic changes, and often generalized retinal dysfunction, despite often having less severe fundus abnormalities on examination. One third of children do not have flecks at presentation. The relatively high proportion of deleterious ABCA4 variants supports the hypothesis that earlier onset disease is often owing to more severe variants in ABCA4 than those found in adult-onset disease.
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