FBN1基因突变致肢端发育不良的研究进展

Advances in acromelic dysplasia caused by FBN1 mutation

FBN1基因突变使其编码的fibrillin-1蛋白异常,影响肌肉骨骼的生长,导致身材高大和身材矮小两种相反的表型,临床表现为马方综合征和肢端发育不良。FBN1突变导致的肢端发育不良疾病包括acromicric发育不良、geleophysic发育不良和Weill-Marchesani综合征,部分位点突变既可导致acromicric发育不良也可导致geleophysic发育不良。TGF-β信号通路失调是不同类型肢端发育不良患者的潜在致病机制。该病目前尚无特效治疗,主要是对症治疗。早期识别症状、明确诊断、早期治疗可改善患者预后。该文将从FBN1突变致肢端发育不良的致病机制、临床表型、治疗和随访等方面进行综述。

The mutation of FBN1 gene results in the abnormality of its encoded fibrillin-1 protein,which affects musculoskeletal growth and results in two opposing phenotypes of tall and short stature,with clinical manifestations of Marfan syndrome and acromelic dysplasia.Acromelic dysplasia caused by FBN1 mutation includes acromicric dysplasia(AD),geleophysic dysplasia(GD)and Weill-Marchesani syndrome(WMS).As some FBN1 mutations have been reported to cause both AD and GD.The dysregulation of TGF-βsignal pathway is the underlying mechanism of acromelic dysplasia.Currently,there is no specific treatment,mainly symptomatic treatment,early identification,diagnosis and treatment will improve prognosis of patients.This article will review the pathogenesis,clinical phenotype,treatment and follow-up of acromelic dysplasia caused by FBN1 mutation.