摘要男性患儿，2岁7个月，因“双眼先天性白内障合并牙齿、面部及神经系统异常2年余”就诊于石家庄市第四医院眼科。患儿主要表现为双眼先天性白内障，既往3月龄行双眼白内障超声乳化抽吸术，2岁行双眼人工晶状体植入+后囊膜切开+前段玻璃体切除术；查体可见锯齿状门牙、耳廓大前倾等典型特殊面容，同时伴智力障碍、言语语言发育障碍及孤独症谱系障碍等罕见神经系统异常。患儿母亲为女性携带者，表现为双眼轻度白内障，以及锯齿状门牙、脸型狭长、鼻梁高凸、耳廓大前倾等特征性面容。家系全基因组测序显示，患儿 NHS基因存在c.3596delA（p.Asn1199Thrfs*6）半合子变异；经Sanger测序进一步验证，患儿母亲及妊娠胎儿均为该变异杂合子。依据相关遗传学指南，该变异因未在千人基因组及gnomAD东亚人群数据库收录（PM2）、携带者表型高度符合单基因病（PP4）、导致蛋白提前终止且符合单倍剂量不足机制（PVS1），被评定为致病性变异（PM2+PP4+PVS1），此变异为该家系的致病原因。结合患儿临床表现及基因检测结果，最终诊断为Nance-Horan综合征。持续给予患儿康复训练以改善神经系统发育问题，随访期间经睫状肌麻痹验光检查，目前予配镜及弱视训练以改善视力。患儿妹妹年幼时发现双眼晶状体点状混浊，目前混浊未进展，部分牙齿略有异常。

abstractsA 2-year-and-7-month-old male child presented to the Department of Ophthalmology, Shijiazhuang Fourth Hospital, with "binocular congenital cataracts combined with dental, facial, and neurological abnormalities for more than 2 years". The child mainly manifested as binocular congenital cataracts. He had previously undergone binocular phacoemulsification and aspiration at 3 months of age, and binocular intraocular lens implantation+posterior capsulotomy+anterior vitrectomy at 2 years of age. Physical examination revealed typical special facial features such as serrated incisors and large, anteverted auricles, along with rare neurological abnormalities including intellectual disability, speech and language developmental disorder, and autism spectrum disorder. The child′s mother was a female carrier, presenting with mild binocular cataracts and characteristic facial features such as serrated incisors, a long and narrow face, a high and prominent nasal bridge, and large, anteverted auricles. Whole-genome sequencing (WGS) of the family showed that the child had a hemizygous variant of c.3596delA (p.Asn1199Thrfs*6) in the NHS gene; further verification by Sanger sequencing confirmed that both the child′s mother and the pregnant fetus were heterozygous for this variant. According to relevant genetic guidelines, this variant was classified as a pathogenic variant (PM2+PP4+PVS1) because it was not recorded in the 1000 Genomes Project or gnomAD East Asian population databases (PM2), the carrier′s phenotype was highly consistent with a monogenic disease (PP4), and it caused premature protein termination and conformed to the haploinsufficiency mechanism (PVS1). This variant was the pathogenic cause of the family. Combining the child′s clinical manifestations and genetic testing results, the final diagnosis was Nance-Horan Syndrome (NHS). The child has been continuously given rehabilitation training to improve neurological development. During follow-up, cycloplegic refraction was performed, and he is currently given glasses and amblyopia training to improve visual acuity. The child′s younger sister was found to have punctate opacities in both crystalline lenses in early infancy; currently, the opacities have not progressed, and some teeth show slight abnormalities.