Clinical and Molecular Characterization of Enhanced S-Cone Syndrome in Children
Clinical and Molecular Characterization of Enhanced S-Cone Syndrome in Children
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DOI：
10.1001/jamaophthalmol.2014.2343
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发表时间：
2014-11-01
影响因子：
8.1
通讯作者：
Moore, Anthony T.
中科院分区：
文献类型：
--
作者：
Hull, Sarah;Arno, Gavin;Moore, Anthony T.
重要性增强的S-视锥综合征（ESCS）是儿童夜盲症鉴别诊断的一部分。目的详细报道一系列ESCS患儿的临床表型和分子遗传学发现。和视网膜成像。主要结果与指标：眼科检查和NR 2 E3基因序列分析结果。结果共纳入5例确诊为ESCS的女孩和4例确诊为ESCS的男孩。所有患者均从儿童早期发展为夜盲症。视力范围为0.00 - 1.20 logMAR（20/20 - 20/320 Snellen）。所有患者均有远视。3例患者沿着拱状有钱币状色素沉着病变，这在成人中是常见的，4例患者沿着拱状有轻度色素沉着障碍或白色，2例患者视网膜外观正常，尽管他们的眼底自发荧光成像显示沿着拱状有自发荧光增加的病灶。3例患者在光学相干断层扫描上有黄斑裂样改变。8例患者在平均8.6岁（年龄范围，3-14岁）时进行了电生理检查，每个患者的结果与ESCS的诊断一致。NR 2 E3的直接测序鉴定了3个先前描述的突变和4个新突变。7例患者复合杂合子突变NR 2 E3，和2个额外的兄弟姐妹患者被假定为纯合子的错义变化的基础上，父母sequencing.CONCLUSIONS和RELEVANCE在这个样本中，儿童ESCS有早发性夜盲症和远视，但没有眼球震颤。根据这项研究，患有ESCS的儿童最初可能表现出正常的眼底外观，但后来沿着拱门发展出斑驳的视网膜色素上皮变化，随后出现相同分布的白色。眼底自发荧光成像在眼底外观正常的儿童中是异常的。电生理检查结果是特异性的，可以进行靶向分子筛选和特异性诊断。
IMPORTANCE Enhanced S-cone syndrome (ESCS) forms part of the differential diagnosis of night blindness in childhood.OBJECTIVE To report in detail the clinical phenotype and molecular genetic findings in a series of children with ESCS.DESIGN, SETTING AND PARTICIPANTS Nine children with ESCS from 5 families underwent full ophthalmic examination, electrophysiological testing, and retinal imaging at a genetic eye disease clinic of a tertiary referral eye hospital. Bidirectional Sanger sequencing of all exons and intron-exon boundaries of NR2E3 was performed.MAIN OUTCOMES AND MEASURES Results of ophthalmic examination and sequence analysis of NR2E3.RESULTS In total, 5 girls and 4 boys with a diagnosis of ESCS were included in the study. All patients had developed nyctalopia from early childhood. Visual acuity ranged from 0.00 to 1.20 logMAR (20/20 to 20/320 Snellen). All patients had hyperopia. Three patients had nummular pigmentary lesions along the arcades as typically seen in adults, 4 patients had mild pigmentary disturbance or white dots along the arcades, and 2 patients had a normal retinal appearance, although their fundus autofluorescence imaging demonstrated foci of increased autofluorescence along the arcades. Three patients had macular schisis-like changes on optical coherence tomography. Eight patients had electrophysiological testing at a mean age of 8.6 years (age range, 3-14 years), and in each patient the findings were consistent with the diagnosis of ESCS. Direct sequencing of NR2E3 identified 3 previously described mutations and 4 novel mutations. Seven patients were compound heterozygous for mutations in NR2E3, and 2 additional sibling patients were presumed to be homozygous for a missense change based on parental sequencing.CONCLUSIONS AND RELEVANCE In this sample, children with ESCS had an early onset of night blindness and hyperopia but no nystagmus. Based on this study, children with ESCS may initially manifest a normal fundus appearance but later develop mottled retinal pigment epithelium change along the arcades, followed by the appearance of white dots in the same distribution. Fundus autofluorescence imaging is abnormal in children with a normal fundus appearance. The electrophysiological findings are pathognomonic and allow targeted molecular screening and a specific diagnosis.