先天性挛缩蜘蛛指畸形的临床及遗传学特点

Clinical and genetic characteristics of congenital contractural arachnodactyly

目的探究先天性挛缩蜘蛛指畸形(congenital contractural arachnodactyly,CCA)的临床特点、遗传学特点及基因-表型相关性。方法选用我中心就诊16例临床诊断为CCA并且存在基因FBN2突变的患者(男8例,女8例),平均年龄5岁。对既往留存患者信息、临床资料、照片、检查结果以及二代测序检测结果进行回顾,分析总结该16例患者的临床表现特征、遗传学特点及二者相关性。结果16例中均存在细长指(趾)(16/16,100%)及手部多发关节挛缩(16/16,100%),存在大关节挛缩体征11例(11/15,73.3%),肌肉发育不良14例(14/16,87.5%),脊柱畸形5例(5/14,35.7%),胸廓畸形6例(6/15,40.0%),卷曲耳16例(16/16,100%),小下颌9例(9/16,56.3%),高腭弓7例(7/11,63.6%)。16例中共发现13种基因FBN2突变,位于外显子区域的错义突变12种,内含子区域突变1种;突变c.2831G>A与c.5200+5G>A为既往文献及相关数据库未报道的新突变位点。突变位点位于外显子26~29者多出现大关节挛缩以及脊柱畸形。结论本组16例CCA发现了2种既往未报道的新位点,并且突变位于外显子26~29时,多出现大关节挛缩以及脊柱畸形。

Objective To investigate the clinical features,genetic characteristics,and genotype-phenotype correlations of congenital contractural arachnodactyly(CCA).Methods Sixteen patients(8 males and 8 females)with a clinical diagnosis of CCA and a mutation of gene FBN2,with a mean age of 5 years,were enrolled in this research.A retrospective study was conducted to review the previous patient information,clinical data,photographs,examination results,and second-generation sequencing test results,and to analyze and summarize the clinical features,genetic characteristics,and genotype-phenotype correlations.Results Of these 16 patients,all had arachnodactyly(16/16,100%)and multiple joint contractures of the hands(16/16,100%),11 had large joint contractures(11/15,73.3%),14 had muscle hypoplasia(14/16,87.5%),5 had kyphosis/scoliosis(5/14,35.7%),6 had pectus deformity(6/15,40.0%),16 had crumpled ears(16/16,100%),9 had micrognathia(9/16,56.3%),and 7 had highly arched palate(7/11,63.6%).Thirteen different kinds of mutations in gene FBN2 were identified in 16 patients,with 12 missense mutations located in exons and 1 mutation in introns.The mutations c.2831G>A and c.5200+5G>A were new mutations not reported before.In addition,this study found that patients with mutations in exons 26-29 are more likely to have large joint contractures and spinal deformities.Conclusions This study summarizes the clinical manifestations of 16 CCA patients and identifies 2 unreported mutations,and patients with mutations in exons 26-29 were more likely to have large joint contractures and spinal deformities.