目的 分析17例软骨发育不全（achondroplasia，ACH）患儿的临床特征及成纤维细胞生长因子受体3（fibroblast growth factor receptor 3，FGFR3）基因变异情况。 方法 回顾性分析2009年1月至2021年10月确诊的17例ACH患儿临床资料及FGFR3基因检测结果。 结果 ACH最常见的临床表现是不匀称型身材矮小（100%，17/17）、大头畸形（100%，17/17）、三叉戟手畸形（82%，14/17）、膝内翻（88%，15/17）。最普遍的影像学是根茎状长骨缩短（100%，17/17）和腰椎椎间距变窄（88%，15/17）。主要并发症有骨骼异常（100%，17/17）、中耳功能障碍（82%，14/17）、运动及语言发育迟缓（88%，15/17）、慢性疼痛（59%，10/17）、睡眠呼吸暂停（53%，9/17）、肥胖（41%，7/17）、枕骨大孔缩小（35%，6/17）、脑积水（24%，4/17）。17例（100%）均存在FGFR3基因变异，13例为FGFR3基因c.1138G>A的热点突变；2例FGFR3基因c.1138G>C变异；2例为未报道的变异，其中1例FGFR3基因c.1252C>T变异，1例FGFR3基因c.445+2_445+5delTAGG变异。 结论 该研究检出FGFR3基因未报道变异位点，扩展了ACH基因变异谱。ACH是一种进行性发展的疾病，其相关并发症由多学科团队协作进行终身管理。
Abstract
Objective To study the clinical features and fibroblast growth factor receptor 3 (FGFR3) gene mutations of children with achondroplasia (ACH) through an analysis of 17 cases. Methods A retrospective analysis was performed on the clinical data and FGFR3 gene detection results of 17 children with ACH who were diagnosed from January 2009 to October 2021. Results Of the 17 children with ACH, common clinical manifestations included disproportionate short stature (100%, 17/17), macrocephaly (100%, 17/17), trident hand (82%, 14/17), and genu varum (88%, 15/17). The common imaging findings were rhizomelic shortening of the long bones (100%, 17/17) and narrowing of the lumbar intervertebral space (88%, 15/17). Major complications included skeletal dysplasia (100%, 17/17), middle ear dysfunction (82%, 14/17), motor/language developmental delay (88%, 15/17), chronic pain (59%, 10/17), sleep apnea (53%, 9/17), obesity (41%, 7/17), foramen magnum stenosis (35%, 6/17), and hydrocephalus (24%, 4/17). All 17 children (100%) had FGFR3 mutations, among whom 13 had c.1138G>A hotspot mutations of the FGFR3 gene, 2 had c.1138G>C mutations of the FGFR3 gene, and 2 had unreported mutations, with c.1252C>T mutations of the FGFR3 gene in one child and c.445+2_445+5delTAGG mutations of the FGFR3 gene in the other child. Conclusions This study identifies the unreported mutation sites of the FGFR3 gene, which extends the gene mutation spectrum of ACH. ACH is a progressive disease requiring lifelong management through multidisciplinary collaboration.
关键词
软骨发育不全 /
成纤维细胞生长因子受体3基因 /
基因变异 /
儿童
Key words
Achondroplasia /
Fibroblast growth factor receptor 3 gene /
Gene mutation /
Child
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