基于发病年龄、淋巴管病变和致病基因的肢体原发性淋巴水肿新分类  

An updated classification of primary lymphedema of extremity based on age of onset,lymphatic anomalies and genetics

作　　者：刘宁飞[1] 高敏哲 Liu Ningfei;Gao Minzhe(Department of Plastic&Reconstructive Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院整复外科,上海200011

出　　处：《中华整形外科杂志》2025年第2期158-167,共10页Chinese Journal of Plastic Surgery

基　　金：国家自然科学基金(81272146)。

摘　　要：目的构建基于发病年龄、淋巴管病变和致病基因的肢体原发性淋巴水肿(PLE)新分类。方法采用前瞻性研究方法,纳入2007年1月至2021年12月于上海交通大学医学院附属第九人民医院整复外科就诊的下肢和上肢PLE患者。记录性别、发病年龄、发病部位、家族史,并进行磁共振淋巴造影(MRL)、吲哚菁绿淋巴造影(ICGL)、核素淋巴造影(LSG)、皮肤组织免疫组化染色、全外显子基因测序。采用描述性方法进行统计分析。结果共纳入1046例患者,其中,累及下肢1013例,上肢33例。按发病年龄分为先天性(<1岁)和迟发性(≥1岁)2类,分别有237例和809例患者,比例约为1∶4。迟发性患者中青春期(11~20岁)发病人数最多,共276例。先天性患者累及单侧上肢33例,累及下肢(单侧和双侧)204例,其中26例(12.7%,26/204)有相关家族史;809例迟发性患者中53例有相关家族史,占6.6%(53/809)。225例患者进行全外显子组测序(下肢208例,上肢17例)显示,37例(17.8%,37/208)下肢PLE患者被检出携带6个基因的38种致病变异,仅1例(5.9%,1/17)上肢PLE患者被检出携带PIEZO1复合杂合子变异。929例下肢和33例上肢PLE患者经过至少1种影像学检查,根据淋巴管功能和形态改变情况,分为3种主要类型的淋巴管异常:以淋巴管延迟或部分显示为特征的节段性淋巴管功能障碍最为常见,与FLT4、GJC2、CELSR1和PTPN14变异相关;淋巴管增生列第2位,与FOXC2和GATA2变异相关;起始淋巴管发育不良或功能障碍列第3位,与FLT4和PIEZO1变异相关。结论本研究提出了基于发病年龄、淋巴管病变和致病基因的肢体PLE 3大分类,即节段性淋巴管功能障碍、淋巴管扩张增生和起始淋巴管发育不良或功能障碍。ObjectiveTo update the classification of extremity primary lymphedema(PLE)based on age of onset,lymphatic anomalies and genetics.MethodsA prospective research method was adopted.Patients with lower and upper limb PLE who visited Department of Plastic&Reconstructive Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine from January 207 to December 2021 were selected.Sex,age of onset,location,family history and morbidity were documented.The lymphatic imaging findings of magnetic resonance lymphography(MRL),indocyanine green lymphography(ICGL)and lymphoscintigraphy(LSG),skin tissue histology and whole exome sequencing were evaluated.Descriptive statistical method was used for data statistics.ResultsA total of 1046 patients were included,among whom 1013 had lower extremity involvement and 33 had upper extremity involvement.Divided by the age of onset,there were 237 cases of congenital(<1 year old)and 809 of late-onset(≥1 year old),with a ratio of about 1∶4.Among the late-onset patients,most patients began to suffer the disease during adolescence(11-20 years old),with a total of 276 cases.Among patients with congenital lower limb PLE,12.7%(26/204)had a family history.Among those with late-onset of PLE,6.6%(53/809)had a family history.A total of 225 patients underwent whole exome sequencing(208 cases in the lower limbs and 17 cases in the upper limbs),showing that 37 patients(17.8%,37/208)with lower limb PLE were found to carry 38 pathogenic variants in FLT4,GJC2,CELSR1,PTPN14,FOXC2 and GATA2,only 1 patient(5.9%,1/17)with upper limb PLE was found to carry a PIEZO1 compound heterozygote variant.Three major lymphatic anomalies were identified,in which segmental lymphatic dysfunction,characterized by delayed or partial demonstration of lymph vessels,was the most common type and associated with FLT4,GJC2,CELSR1,and PTPN14 mutations.The second most common type was lymphatic hyperplasia,which was associated with FOXC2 and GATA2 variants,followed by initial lymphatic aplasia or dysfun

关 键 词：淋巴水肿 原发性淋巴水肿 淋巴管功能障碍 淋巴管扩张增生 起始淋巴管发育不良或功能障碍 淋巴造影 

分 类 号：R73[医药卫生—肿瘤]