Papillorenal综合征一个家系报告并文献复习

目的探讨Papillorenal综合征[又称肾-视神经盘缺损综合征(renal coloboma syndrome)]患儿的临床表现特征和基因变异特点。方法收集华中科技大学同济医学院附属武汉儿童医院2018年2月确诊,PAX2突变导致的Papillorenal综合征一个家系的临床表现、影像学检查及基因检测等资料。以"PAX2"和"肾-视神经盘缺损"、"Papillorenal syndrome"和"renal coloboma syndrome"为关键词,检索1995年4月至2018年4月中国期刊全文数据库、万方数据知识服务平台、PubMed、人类基因组突变数据库收录论文,总结PAX2基因变异导致Papillorenal综合征患者的临床表型及基因型特点。结果患儿女,10岁2个月。因"全身水肿伴尿量减少1周"入院。实验室检查血BUN25.30mmol/L,Scr766.5μmol/L,尿蛋白量3.6g/24h。影像学检查提示双侧膀胱、输尿管反流,合并左侧重复肾、重复输尿管,右侧髋关节发育不良。患儿父亲确诊慢性肾脏病10年,血液透析6年。父女两人均有视神经盘异常。基因检测发现父女两人同时携带PAX2杂合无义突变c.219C>G(p.Y73X)。未检索到相关报道的中文文献。英文文献94篇,有177例Papillorenal综合征患者得到基因检测确诊,共有92种PAX2变异被报道,其中有10个为无义突变。未见Papillorenal综合征合并关节发育异常的报道。结论PAX2突变导致的Papillorenal综合征主要表现为肾脏和视神经发育异常,可伴有其他系统异常,髋关节发育不良可能为Papillorenal综合征新表型。

Report of papillorenal syndrome in a family and literature review

Objective To investigate the clinical manifestations and genetic features of children with papillorenal syndrome caused by PAX2 gene mutation. Methods Clinical manifestations, imaging changes and sequencing data were collected and analyzed from a family with papillorenal syndrome who were diagnosed in Wuhan Children's Hospital in February 2018. "PAX2", "papillorenal syndrome" and "renal coloboma syndrome" were used as key words to search in China National Knowledge Infrastructure, Wangfang Data Knowledge Service Platform, PubMed and Human Gene Mutation Database up to April 2018. Results A ten years old girl was admitted due to "edema and urine output decreased for one week". Lab showed BUN 25.30 mmol/L, Scr 766.5 μmol/L, Urine protein 3.6 g/24 h. Imaging examination showed bilateral vesical and ureter reflux combined with left duplex kidney and duplication of ureter. Developmental dysplasia of the left hip was also found. The father of the patient had been diagnosed with chronic kidney disease for 10 years and on hemodialysis for 6 years. Next generation sequencing revealed that both the father and daughter carried a heterozygous nonsense mutation in the exon3 c.219C＞G(p.Y73X) of PAX2. No Chinese literature ever was reported about papillorenal syndrome. Ninety-four articles in English were retrieved and 177 patients with papillorenal syndrome were confirmed by gene analysis with a total of 92 PAX2 variants. Ten nonsense mutations had been reported. Developmental dysplasia of the hip (DDH) never be reported before. Conclusion Papillorenal syndrome caused by PAX2 mutation can mainly manifest as abnormal development of both kidney and optic nerve, which may be accompanied by other systemic abnormalities, it is rarely reported in China. DDH may be a new phenotype of papillorenal syndrome.