胶原ⅩⅩⅦ α1型基因突变所致Steel综合征1例并文献分析

Steel syndrome caused by collagen type ⅩⅩⅦ α1 chain mutation:a case report and literature review

目的探讨胶原ⅩⅩⅦα 1型(COL27A1)基因突变所致Steel综合征的临床特征、诊断、基因检测、治疗及预后。方法报告海军军医大学(第二军医大学)长海医院骨科收治的1例汉族Steel综合征合并脊柱侧凸青少年患者资料,同时利用PubMed数据库以"Steel syndrome" AND "COL27A1"为主题词检索1993年1月至2020年10月相关文献,共检索到13篇文献(共54例Steel综合征患者),纳入其中全外显子测序确诊的COL27A1突变所致Steel综合征患者17例。对包括本例在内共18例COL27A1突变所致Steel综合征患者的临床特征进行分析。结果本例患者除有发育迟缓、腕骨融合、脊柱侧凸、长椭圆脸、前额突出、鼻前倾等常见临床表现外,还有蹼状颈和颈后低发际线等特殊表现。全外显子测序提示COL27A1存在2个复合杂合突变位点:p.Pro705Ser和p.Asn1723Ser,分别来源于父亲和母亲。综合各项检查和全外显子测序结果,确诊Steel综合征合并先天性脊柱侧凸。患者完善术前检查后行脊柱侧凸后路三维矫形植骨融合内固定术,手术节段T3~L1。术后3个月、1年、2年门诊复查全脊柱正侧位X线片示固定节段骨性融合良好,无断钉、断棒、交界性后凸、远端附加现象等并发症。18例患者中男9例、女9例,确诊年龄为0.17~14岁,3例为COL27A1复合杂合突变(1例p.Pro705Ser和p.Asn1723Ser、1例c.93del和c.3075del、1例p.Cys174Serfs^*34和p.Arg707^*),15例为纯合错义突变(11例p.Gly697Arg、1例p.Gly802Glu、1例p.Gly904Arg、1例c.4261-1G>A、1例c.3556-2A>G)。1例患者临床特征不详,余17例主要临床表现有脊柱侧凸(17例)、身材矮小(12例)、长椭圆脸(9例)、前额突出(9例)、发育迟缓(5例)、听力受损(5例)等;18例患者的影像学特征有髋关节脱位(16例)、桡骨头脱位(11例)、腕骨融合(9例)等。结论 COL27A1突变导致的Steel综合征是一种罕见的常染色体隐性遗传病,患者家族史、临床特征、影像学检查等仅能为该综合征提供倾向性诊断,最终确诊需要依据基因检测结果。对于该病的治疗应加强研究以改善预后。

Objective To investigate the clinical features,diagnosis,gene detection,treatment and prognosis of Steel syndrome caused by the mutation of collagen typeⅩⅩⅦα1 chain(COL27A1).Methods A case of Han adolescent Steel syndrome complicated with scoliosis in the Department of Orthopaedics,Changhai Hospital,Naval Medical University(Second Military Medical University)was reported.Altogether 13 related articles(54 cases of Steel syndrome)from Jan.1993 to Oct.2020 were retrieved by using"Steel syndrome"AND"COL27A1"as subject word in the PubMed database.Among them,17 cases of Steel syndrome caused by COL27A1 mutation and confirmed by whole exome sequencing were included.The clinical features of the 18 patients with Steel syndrome caused by COL27A1 mutation were analyzed.Results In this case,in addition to common clinical manifestations such as developmental delay,carpal coalition,scoliosis,long oval-shaped face,prominent forehead,anteverted nares and other common clinical manifestations,the patient also had webbed neck and low hairline at the back of neck.Whole exome sequencing indicated that COL27A1 gene had two compound heterozygous mutations:p.Pro705Ser and p.Asn1723Ser,which originated from father and mother,respectively.The diagnosis of Steel syndrome with congenital scoliosis was confirmed by the results of all examinations and the whole exome sequencing.After the preoperative examination,the patient was treated with posterior three-dimensional orthopaedic bone graft fusion and internal fixation(surgical segments T3-L1).The anteroposterior and lateral X-rays of the full spine of the patient were performed in the outpatient department at 3 months,1 year and 2 years after the operation.The results showed satisfactory segmental fusion without complications such as fracture of screws and rods,junctional kyphosis and distal adding-on phenomenon.Among the 18 patients,there were nine males and nine females,with a diagnosis age of 0.17-14 years.Three were COL27A1 complex heterozygous mutations,including p.Pro705Ser and p.Asn1723Ser(one case),c.93del and c.3075del(one case),and p.Cys174Serfs^*34 and p.Arg707^*(one case);15 were homozygous missense mutations,including p.Gly697Arg(11 cases),p.Gly802Glu(one case),p.Gly904Arg(one case),c.4261-1G>A(one case),and c.3556-2A>G(one case).The main clinical features(unknown in one patient)included scoliosis(17 cases),short stature(12 cases),long oval-shaped face(nine cases),prominent forehead(nine cases),developmental delay(five cases),hearing loss(five cases),etc.The imaging features of the 18 patients included hip dislocation(16 cases),radial head dislocation(11 cases),carpal coalition(nine cases),etc.Conclusion Steel syndrome caused by COL27A1 mutation is a rare autosomal recessive genetic disease.Its family history,clinical features and imaging examinations provide a preferential diagnosis,but the final diagnosis should be based on the result of gene sequencing.The treatment of this disease should be further researched to improve the prognosis.