Miraldi Utz Virginia, Pfeifer Wanda, Longmuir Susannah Q, Olson Richard John, Wang Kai, Drack Arlene V
Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
JAMA Ophthalmol. 2018 Apr 1;136(4):389-398. doi: 10.1001/jamaophthalmol.2018.0185.
Congenital stationary night blindness (CSNB) implies a stable condition, with the major symptom being nyctalopia present at birth. Pediatric clinical presentation and the course of different genetic subtypes of CSNB have not, to our knowledge, been well described in the era of molecular genetic diagnosis.
To describe the presentation and longitudinal clinical characteristics of pediatric patients with molecularly confirmed TRPM1-associated complete CSNB (cCSNB).
DESIGN, SETTING, PARTICIPANTS: This study was conducted at the University of Iowa from January 1, 1990, to July 1, 2015, and was a retrospective, longitudinal case series of 7 children (5 [71.4%] female) with TRPM1-associated cCSNB followed up for a mean (SD) of 11.1 (2.8) years.
History, ophthalmologic examination findings, full-field electroretinogram (ffERG) results, full-field stimulus threshold testing results, Goldmann visual field results, optical coherence tomography results, and molecular genetic results were evaluated. Presenting symptoms and signs, the correlation of refractive error with electroretinography, and clinical evolution were analyzed.
Seven patients (5 [71.4%] female) presented early in childhood with strabismus (n = 6 [86%]), myopia (n = 5 [71%]), and/or nystagmus (n = 3 [43%]). The mean (SD) age at presentation was 8 (4) months and for receiving a diagnosis by ffERG was 7.3 years, with molecular diagnosis at 9.7 years. The mean (SD) length of follow-up was 11 (2.8) years. The best-corrected visual acuity at the most recent visit averaged 20/30 in the better-seeing eye (range, 20/20-20/60). The mean (SD) initial refraction was -2.80 (4.42) diopters (D) and the mean refraction at the most recent visit was -8.75 (3.53) D (range, -4.00 to -13.75 D), with the greatest rate of myopic shift before age 5 years. Full-field electroretinogram results were electronegative, consistent with cCSNB, without a significant change in amplitude over time. No patient or parent noted night blindness at presentation; however, subjective nyctalopia was eventually reported in 5 of 7 patients (71%). The full-field stimulus threshold testing results were moderately subnormal (-29.7 [3.8] dB; normal -59.8 [4.0] dB). Goldmann visual field results were significant for full I-4e, but constricted I-2e isopter. Eight different mutations or rare variants in TRPM1 predicted to be pathogenic were detected, with 3 novel variants.
Children with TRPM1-associated cCSNB presented before school age with progressive myopia as well as strabismus and nystagmus (but not nyctalopia), with stable, electronegative ffERG results, mildly subnormal full-field stimulus threshold testing results, and a constricted I2e isopter on perimetry. These findings suggest that ffERG and cCSNB genetic testing should be considered for children who present with early-onset myopia, especially in the presence of strabismus and/or nystagmus, and that TRPM1-associated cCSNB is a channelopathy that may present without complaints of night blindness in childhood.
先天性静止性夜盲（CSNB）意味着病情稳定，主要症状是出生时即存在夜盲。据我们所知，在分子遗传学诊断时代，CSNB不同基因亚型的儿科临床表现及病程尚未得到充分描述。
描述经分子确诊的与TRPM1相关的完全性CSNB（cCSNB）儿科患者的临床表现及纵向临床特征。
设计、地点、参与者：本研究于1990年1月1日至2015年7月1日在爱荷华大学进行，是一项对7例与TRPM1相关的cCSNB儿童（5例[71.4%]为女性）的回顾性纵向病例系列研究，平均（标准差）随访11.1（2.8）年。
评估病史、眼科检查结果、全视野视网膜电图（ffERG）结果、全视野刺激阈值测试结果、Goldmann视野结果、光学相干断层扫描结果及分子遗传学结果。分析首发症状和体征、屈光不正与视网膜电图的相关性以及临床演变情况。
7例患者（5例[71.4%]为女性）在儿童早期出现斜视（n = 6例[86%]）、近视（n = 5例[71%]）和/或眼球震颤（n = 3例[43%]）。首发时的平均（标准差）年龄为8（4）个月，通过ffERG确诊的平均年龄为7.3岁，分子诊断的平均年龄为9.7岁。平均（标准差）随访时间为11（2.8）年。最近一次就诊时，较好眼的最佳矫正视力平均为20/30（范围为20/20 - 20/60）。初始平均（标准差）屈光度为-2.80（4.42）屈光度（D），最近一次就诊时的平均屈光度为-8.75（3.53）D（范围为-4.00至-13.75 D），近视度数在5岁前增长最快。全视野视网膜电图结果为阴性，与cCSNB一致，随时间振幅无显著变化。首发时无患者或家长提及夜盲；然而，最终7例患者中有5例（71%）报告有主观夜盲。全视野刺激阈值测试结果中度低于正常（-29.7 [3.8] dB；正常为-59.8 [4.0] dB）。Goldmann视野结果显示I - 4e完全缺损，但I - 2e等视线收缩。在TRPM1中检测到8种预测为致病性的不同突变或罕见变异，其中3种为新变异。
与TRPM1相关的cCSNB儿童在学龄前期出现进行性近视以及斜视和眼球震颤（但无夜盲），ffERG结果稳定且为阴性，全视野刺激阈值测试结果轻度低于正常，视野检查I2e等视线收缩。这些发现表明，对于早发性近视儿童，尤其是伴有斜视和/或眼球震颤的儿童，应考虑进行ffERG和cCSNB基因检测，并且与TRPM1相关的cCSNB是一种在儿童期可能无夜盲主诉的通道病。
