Wolf-Hirschhorn综合征11例临床分析

Clinical analysis of 11 cases with Wolf-Hirschhorn syndrome

目的 探讨Wolf-Hirschhorn综合征(WHS)的临床表现、遗传学特征、治疗及预后等。方法 回顾分析2009年6月-2018年6月诊治的11例WHS患儿的临床资料。结果 符合WHS染色体改变诊断标准者15例,其中男6例、女9例,就诊年龄中位数为4月龄。15例患儿的染色体检测均有4p结构畸变,主要为单纯4p缺失(46.6%),其他还存在臂间倒位、重复或插入、衍生染色体、环状染色体。其中3例进一步行基因检测确认缺失片段大小。15例中11例资料完整,临床表现明确。首诊原因包括癫痫5例,生后反应差、低体质量5例,肺炎1例。主要核心临床表现为生长/精神发育迟缓、癫痫、希腊武士头盔面容,还可能存在多系统异常。3例在1岁内因肺炎/惊厥死亡,存活者均存在严重智力运动发育落后。结论WHS为4号染色体的结构畸变,4p16.3上的关键基因缺失,导致生长/精神发育迟缓、癫痫、特殊面容、多系统异常,预后较差。

Objective To investigate clinical features, genetic trait and treatment and prognosis of children with Wolf- Hirschhorn syndrome (WHS). Methods Clinical data of 11 children with WHS enrolled between June 2009 to June 2018 was retrospectively analyzed. Results A total 15 cases (6 males and 9 females) met chromosome abnormalities diagnostic criteria, and the median age of children receiving medication for the first time was 4 months. Chromosomal analysis of 15 patients showed that most WHS individuals (46.6%) had pure 4p terminal deletions, and others had pericentric inversion and duplication/ insert and derivative and ring chromosome 4. Among them, 3 cases received further genetic testing to confirm the size of deletion. 11/15 children's clinical manifestations had been collected integrally, and the onset symptom of 5 cases was epilepsy, 5 cases poor neonatal reflex or low weight, and 1 case pneumonia. The main clinical manifestations included growth/ mental retardation, epilepsy and the “Greek warrior helmet” appearance. In addition, there were other multiple congenital anomalies. Three cases died of pneumonia and convulsions in the first years of life, the survivors all had severe psychomotor retardation. Conclusion WHS is a structural aberration of chromosome 4 which is featuring as “growth/mental retardation, epilepsy, special face and multiple congenital anomalies” caused by critical gene fragments loss in this segment. WHS has a poor prognosis.