Department of Pediatrics, Radboud University Medical Center Amalia Children's hospital, P.O. Box, 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Eur J Pediatr. 2018 Aug;177(8):1293-1298. doi: 10.1007/s00431-018-3183-1. Epub 2018 Jun 9.
The aim of this retrospective study is to describe ocular findings in a large Noonan syndrome cohort and to detect associations between ocular features and genetic mutations that were not found in earlier studies. We collected ophthalmological and genetic data of 105 patients (median age, 12 years; range, 0-60 years) clinically diagnosed as Noonan syndrome. The ocular findings were linked to the genotypes. All patients with Noonan syndrome showed multiple abnormalities in the categories of vision and refraction, external ocular features, ocular alignment and motility, anterior ocular segment, and posterior ocular segment. In total, 50 patients have NS due to a mutation in PTPN11. Permanent visual impairment (bilateral best-corrected visual acuity < 0.3) was found in 7 patients, including patients with a mutation in RAF1, SHOC2, and KRAS. Keratoconus was found in 2 PTPN11 positive patients, and prominent corneal nerves were observed in a patient with a SOS1 mutation.
This study shows an overview of ocular abnormalities in Noonan syndrome, including permanent visual impairment caused by binocular optic nerve abnormalities and nystagmus. Delay in ophthalmological diagnosis is still present, also in patients with visual impairment. All Noonan syndrome patients should have a complete ophthalmological examination at the time of diagnosis. What is Known: • Although we discover more pathogenic mutations in patients with Noonan syndrome, Noonan syndrome still is a clinical diagnosis • Ocular features of Noonan syndrome are characterized by developmental anomalies of the eyelids and associated with other ocular abnormalities in childhood (including refractive errors, strabismus and amblyopia). What is New: • There seems to be a delay in the ophthalmological diagnosis and awareness of the broad variety ofophthalmological features including refractive errors and visual impairment in Noonan syndrome is needed. All children should have a full ophthalmological examination at the time of diagnosis. • Permanent visual impairment (best-corrected visual acuity < 0.3) is found in patients with mutations in RAF1, SHOC2, and KRAS and the cause is probably a developmental disorder of the optic nerves.
本回顾性研究旨在描述大样本努南综合征患者的眼部表现，并发现以前研究未发现的眼部特征与基因突变之间的关联。
我们收集了 105 例临床诊断为努南综合征患者的眼科和遗传数据（中位年龄 12 岁，范围 0-60 岁）。将眼部发现与基因型相关联。所有努南综合征患者在视力和屈光度、眼球外部特征、眼球对齐和运动、眼前节和眼后节等类别中均显示出多种异常。共有 50 例患者因 PTPN11 突变而患有 NS。7 例患者存在永久性视力损害（双眼最佳矫正视力<0.3），包括 RAF1、SHOC2 和 KRAS 突变患者。2 例 PTPN11 阳性患者存在圆锥角膜，1 例 SOS1 突变患者存在明显的角膜神经。
本研究全面描述了努南综合征的眼部异常，包括由双眼视神经异常和眼球震颤引起的永久性视力损害。眼科诊断的延迟仍然存在，在视力受损的患者中也是如此。所有努南综合征患者在诊断时均应进行全面的眼科检查。
尽管我们在努南综合征患者中发现了更多的致病性突变，但努南综合征仍然是一种临床诊断。努南综合征的眼部特征表现为眼睑发育异常，并伴有儿童时期的其他眼部异常（包括屈光不正、斜视和弱视）。
似乎存在眼科诊断的延迟，需要提高对努南综合征广泛的眼部特征（包括屈光不正和视力损害）的认识。所有儿童在诊断时都应进行全面的眼科检查。永久性视力损害（最佳矫正视力<0.3）见于 RAF1、SHOC2 和 KRAS 突变患者，其原因可能是视神经发育障碍。
