Majander Anna, Bowman Richard, Poulton Joanna, Antcliff Richard J, Reddy M Ashwin, Michaelides Michel, Webster Andrew R, Chinnery Patrick F, Votruba Marcela, Moore Anthony T, Yu-Wai-Man Patrick
UCL Institute of Ophthalmology, London, UK.
Moorfields Eye Hospital, London, UK.
Br J Ophthalmol. 2017 Nov;101(11):1505-1509. doi: 10.1136/bjophthalmol-2016-310072. Epub 2017 Mar 17.
The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup.
Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m.3460G>A, m.11778G>A or m.14484T>C.
In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3-15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m.3460G>A and m.14484T>C mutations compared with the m.11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) ≥0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA <0.05 in their better seeing eye.
Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor.
Leber遗传性视神经病变（LHON）在儿童期发病相对罕见。本研究描述了在这一特定LHON亚组中观察到的临床和分子遗传学特征。
我们的回顾性研究包括一个由27例患者组成的英国儿童LHON队列，以及通过对文献进行系统综述确定的另外69例病例。如果视力丧失发生在12岁及以下且存在确诊的致病性线粒体DNA突变：m.3460G>A、m.11778G>A或m.14484T>C，则纳入患者。
在英国儿童LHON队列中，观察到三种视力丧失和进展模式：（1）经典急性型（17/27，63%）；（2）缓慢进展型（4/27，15%）；（3）隐匿性或亚临床型（6/27，22%）。隐匿性起病的儿童诊断延迟3至15年。与m.11778G>A突变相比，携带m.3460G>A和m.14484T>C突变的患者自发视力恢复更为常见。基于对67例有可用视力数据患者的荟萃分析，26例（39%）患者至少一只眼的最终最佳矫正视力（BCVA）≥0.5 Snellen小数视力，而13例（19%）患者较好眼的最终BCVA<0.05。
尽管儿童期发病的LHON视力预后相对较好，但在英国，约五分之一的患者仍将符合法定失明的视力标准。临床表现可能隐匿，当面对不明原因视力低于正常且视盘苍白的儿童时，鉴别诊断应考虑LHON。
