[Clinical manifestation and gene analyses of 15 patients with intellectual disability or developmental delay complicated with congenital nystagmus].

Objective: To analyze the clinical and genetic features of 15 cases with intellectual disability or developmental delay (ID/DD) complicated with congenital nystagmus. Method: The clinical characteristics and the results of laboratory tests, images and genetics of 15 patients with ID/DD complicated with congenital nystagmus, confirmed by gene diagnosis in the Department of Neurology, Children's Hospital Affiliated to Capital Institute of Pediatrics from March 2015 to October 2016, were retrospectively analyzed. The physiological function of 13 disease genes and the molecular signaling pathways were also comparatively studied. Result: The patients included 11 males and four females, with an age of 2 months-15 years (median age 27 months). The result of multiplex ligation-dependent probe amplification was positive in two patients only with hypomyelination on head MRI. Positive results were found in 13 patients with or without abnormal head MRI or other deformities using targeted capture technology and next generation sequencing. Two patients were diagnosed with Pelizaeus-Merzbacher disease, two had hypomyelination with an atrophy of the basal ganglia and cerebellum and two had oculocutaneous albinism. Pelizaeus-Merzbacher-like disease was found in one case, cerebro-oculo-facio-skeletal syndrome in one case, Rubinstein-Taybi syndrome in one case, mental retardation type 5 in one case, methylmalonic aciduria combined with hyperhomocysteinemia in 1 case, ataxia telangiectasia in one case, hypomyelinating leukodystrophy type 8 in one case, Marinesco-Sjögren syndrome in one case and CHARGE syndrome in one case. A total of 12 novo mutations were reported in this study. Conclusion: The causes of children with ID/DD complicated with congenital nystagmusis are complex. Comprehensive clinical and auxiliary examinations should be performed to improve the accuracy of the diagnosis. Reasonable application of different genetic testing methods can significantly improve the diagnostic accuracy of molecular genetic etiology in children with ID/DD.目的： 分析15例智力障碍或发育迟缓伴先天性眼球震颤患儿的临床及遗传学特点。 方法： 回顾性分析2015年3月至2016年10月首都儿科研究所附属儿童医院收治的经基因检测确证的15例病因不同的智力障碍或发育迟缓伴先天性眼球震颤患儿的临床资料、实验室、影像学以及遗传学检查结果，并对13个致病基因的生理功能及分子信号通路进行比较研究。 结果： 15例患儿中男11例、女4例，年龄2月龄至15岁（中位数27月龄）。2例仅伴头颅核磁髓鞘化落后的患儿多重连接探针扩增检查结果阳性，13例伴或不伴头颅核磁异常或其他畸形的患儿靶向捕获二代测序结果阳性。15例患儿中确诊佩梅病2例，伴基底节小脑萎缩的髓鞘发育不良2例，眼皮肤白化病2例，佩梅样病1例，脑眼面骨骼综合征1例，Rubinstein-Taybi综合征1例，精神发育迟滞5型1例，甲基丙二酸血症合并高同型半胱氨酸血症1例，共济失调毛细血管扩张症1例，髓鞘形成不良性脑白质营养不良8型1例，Marinesco-Sjögren综合征1例，CHARGE综合征1例，其中共发现了12种国外未报道的新突变。 结论： 智力障碍或发育迟缓伴先天性眼球震颤患儿的病因复杂，应进行全面的临床及辅助检查以提高诊断的准确性，不同遗传学检查方法的合理应用可以明显提高智力障碍或发育迟缓患儿的分子遗传学病因诊断率。.