186例Kindler综合征临床和基因突变分析  

Clinical Characteristics and Gene Mutations in 186 Cases of Kindler Syndrome

作　　者：闪莹 左亚刚 SHAN Ying;ZUO Yagang(Department of Dermatology,State Key Laboratory of Complex Severe and Rare Diseases,PUMC Hospital,CAMS and PUMC,National Clinical Research Center for Dermatologic and Immunologic Diseases,Beijing 100730,China;Graduate School,Hebei North University,Zhangjiakou,Hebei 075000,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院皮肤科,疑难重症及罕见病国家重点实验室国家皮肤与免疫疾病临床医学研究中心,北京100730 [2]河北北方学院研究生院,河北张家口075000

出　　处：《中国医学科学院学报》2022年第2期227-235,共9页Acta Academiae Medicinae Sinicae

摘　　要：目的总结Kindler综合征(KS)的临床表现及基因突变特点,为该类疾病的诊疗提供理论依据。方法汇总分析北京协和医院收治的1例FERMT1基因新突变导致的KS病例和国内外报道的185例患者的临床资料,包括基因类型、临床特点及其并发肿瘤发生的年龄、部位和类型等。结果共收集186例KS患者,男110例、女76例,平均年龄(28±16)岁,其中151例报道了基因突变位点,94例报道了详细的临床表现。KS的主要临床表现有皮肤异色症、童年水疱史、光敏感,次要临床表现有口腔内炎症、掌跖角化、假性并指、吞咽困难、尿道狭窄等。其中口腔内炎症(r=0.234,P=0.023)、掌跖角化(r=0.325,P=0.001)、假性并指(r=0.247,P=0.016)、吞咽困难(r=0.333,P=0.001)、尿道狭窄(r=0.280,P=0.006)与年龄具有显著相关性,32岁以上患者发生概率明显增高。尿道狭窄(χ^(2)=11.292,P=0.001)、肛门狭窄(χ^(2)=4.014,P=0.045)与性别具有显著相关性,男性多于女性。151例患者中发现80种不同的基因突变位点,其中最常见的基因突变位点为c.676C>T。27例KS患者发生41例次肿瘤,鳞状细胞癌占92.7%。鳞状细胞癌发病率与患者所处国别与基因突变位点之间无相关性。结论KS是罕见的先天性大疱性表皮松解症,以FERMT1基因c.676C>T突变最常见,易发生鳞状细胞癌,曝光部位(手、口唇)为主要的发病部位。Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS.Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected.The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed.Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years.The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively.The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ^(2)=11.292,P=0.001)and anal stenosis(χ^(2)=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%.The gene mutation site had no significant correlation with squamous cell carcinoma or patient country.Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).

关 键 词：Kindler综合征 下唇肿物 鳞状细胞癌 隐性遗传性疾病 伴大疱的先天性皮肤异色症 

分 类 号：R758.59[医药卫生—皮肤病学与性病学]