SPEN基因变异致Radio-Tartaglia综合征一例报告并文献复习

Radio-Tartaglia Syndrome Caused by SPEN Gene Mutation:A Case Report and Literature Review

目的分析Radio-Tartaglia综合征(OMIM#619312)的临床表现及遗传学特征。方法回顾分析1例确诊为Radio-Tartaglia综合征患儿(OMIM#619312)的临床和分子遗传学检测资料。并以“Radio-Tartaglia syndrome”或“Radio-Tartaglia综合征”或“SPEN gene”或“SPEN基因”为关键词在PUBMED、万方数据库、维普检索平台进行文献复习。结果患儿,男,4岁,主要表现为全面发育迟缓,语言延迟。头围较小,窄额头,高低眉,睑裂倾斜,高弓腭。全外显子基因测序显示患儿SPEN基因(Chr1:15932638)新发(De novo)可解释患者表型的致病性变异NM_015001.3:exon11:c.6398T>A(p.Leu2133*),结合临床表现和基因检测结果,确诊为Radio-Tartaglia综合征。检索到相关文献16篇,SPEN变异88例,涉及错位变异、缺失变异、重复变异和插入变异。结论本例研究发现了Radio-Tartaglia综合征的新的SPEN基因变异点c.6398T>A(p.Leu2133*)。临床诊疗中,全身发育迟缓伴有智力障碍、言语迟缓和各种行为异常伴颅面部畸形的情况,可考虑此病,应建议家属早日进行基因检测以明确诊断,以便及时进行多学科综合干预,以促进患儿全面发育。

Objective To analyze the clinical features and genetic variation of patients with Radio-Tartaglia syndrome.Methods The clinical and molecular genetic data of a child diagnosed with Radio-Tartaglia syndrome were retrospectively reviewed.Clinical data of other 34 patients diagnosed with Radio-Tartaglia syndrome were also reviewed.Results:The patient was a 4-year-old boy with global developmental delay,speech delay and craniofacial dysmorphism:a narrow forehead,high-arched palate,slanting eyes.Genetic tests of the patient and his parents were conducted for further diagnosis,the result suggested a pathological mutation(De novo)in SPEN gene:NM_015001.3:exon11:c.6398T>A(p.Leu2133*).Thus,a Radio-Tartaglia syndrome diagnosis was concluded.Conclusion Radio-Tartaglia syndrome is a rare neurodevelopmental disorder caused by de novo truncating mutation in SPEN gene,characterized by global developmental delay with impaired intellectual development,speech delay,variable behavioral abnormalities,autistic features,CHD and craniofacial dysmorphism.Brain imaging may show nonspecific defects;rare patients have seizures or pyramidal signs.No cure has been found by now,which calls for attention of the clinicians and researches.Follow-ups are needed for the prodiognosis and timely interventions for the patients.We have discovered a new pathogenic variance in SPEN gene,c.6398T>A(p.Leu2133*)leading to Radio-Tartaglia syndrome in this study.